Psychopharmacology is the study of drugs used to treat psychiatric disorders. It discusses many psycho-active medications that alter synaptic transmission in the brain in certain and specific ways. Medications that affect psychic function, behavior or experience are called psychotropic medications. They have significant effect on higher mental functions. Psychopharmacological agents are firstline treatment for almost all psychiatric ailments nowadays. Within the growing availability of a wide range of drugs to treat mental illness.
The invention of psychotherapeutic drugs has enacted a major change in the management of patient. The drugs are very effective in controlling the symptoms and return the patient to the community. Various drugs in psychiatry are called as psychotropic or psycho-active drugs.
Historically reaction to and treatment of the mentally ill ranged from begin involvement to intervention some would consider inhumane. Individuals with mental illness were feared because of common beliefs associate them with demons or the supernatural.
Beginning in the late 18th century, a type of ‘moral reform’ in the treatment of persons with mental illness began to occur. This resulted in the establishment of community and state hospitals concerned with the needs of persons with mental illness. The early part of the 20th century scout the advent of the somatic therapies in psychiatry. Individuals with mental illness were treated with insulin shock therapy, wet sheet packs, ice baths, electroconvulsive therapy and psychosurgery prior to 1950, sedative and amphetamines were the only significant psychotropic medications available.
Since 1950s, the development of psychopharmacology has expanded to include widespread use of antipsychotic, antidepressant, and antianxiety medications.
CLASSIFICATION OF PSYCHOTROPIC DRUGS
- Mood-stabilizing drugs
- Anxiolytics and hypnosedatives
- Antiepileptic drugs
- Antiparkinson drugs
- Miscellaneous drugs which include stimulants, drugs used in eating disorders, drugs used in deaddiction, drugs used in child psychiatry, vitamins, calcium channel blockers, etc.
Antipsychotic agents are also known as neuroleptics, major tranquilizers or phenothiazines, this group of drugs has a major clinical use in the treatment of psychosis. Psychosis is a state in which a person's ability to recognize reality, to communicate and to relate to others is severely impaired (Wilson HA Kheisel).
The antipsychotic drugs are used to reduce the psychomotor excitement and control some symptoms of schizophrenia without causing disinhibition, confusion, sleep, hypnosis or anesthesia. The alternative terms of these drugs are neuroleptics, antischizophrenic, major tranquilizers.
The main therapeutic use of antipsychotic drug is to reduce hallucination, delusion, agitation, and psychomotor excitement in schizophrenia, organic psychosis and mania.
Antipsychotic drugs do not cure mental illness, but they calm the patient, relieve them, activate the immobile and withdrawn, and make some more accessible to psychotherapy.
Antipsychotics are those psychotropic drugs, which are used for the treatment of psychotic symptoms. These are also known as neuroleptics as they produce neurological side effects, major tranquilizers, D2-receptor blockers and antischizophrenic drugs. This group of drugs are used to control the symptoms of psychosis. These drugs produce calming effect without significantly sedating the client.
For example: A typical antipsychotics = serotonin-dopamine antagonist. Namely as— Haloperidol (haldol), Chlorpromazine (Thorazine).
Antipsychotic drugs are a class of medicines used to treat psychosis and other mental and emotional conditions.
The original antipsychotic drugs were happened upon largely by chance and were tested empirically for their effectiveness.
The first antipsychotic was chlorpromazine, which was developed as a surgical anesthetic, it was first used on psychiatric patients in the belief that it would have a calming effect. It was introduced for the treatment of psychosis during the period when lobotomy was a common treatment and was hailed as a ‘cure’ for schizophrenia. It was then touted to provide a ‘chemical lobotomy’, causing similar neurological effects without requiring surgery.
|CLASSIFICATION OF ANTIPSYCHOTIC DRUGS|
300 – 1500
50 – 100 IM only
100 – 400
30 – 60 IM only
300 – 800
1 – 5 IM
25 – 50 IM
every 1 – 3 weeks
3 – 40
5 – 100
4 – 20
20 – 60 Weekly
50 – 225
25 – 100
50 – 400
2 – 10
10 – 20 mg
150 – 750
20 – 80 mg
0.5 – 50
Common conditions with which antipsychotics might be used include schizophrenia, mania and delusional disorder. They might be used to counter psychosis associated with a wide range of other diagnosis. Antipsychotics may also be used in mood disorder (e.g. bipolar disorder) even when no signs of psychosis are present.
- Organic Psychiatric Disorders
- Delirium tremens
- Drug-induced psychosis and other organic mental disorders.
- Functional Disorders
- Schizoaffective disorders
- Paranoid disorders.
- Mood Disorders
- Major depression with psychotic symptoms.
- Childhood Disorders
- Attention–deficit hyperactivity disorder
- Conduct disorder.
- Neurotic and Other Psychiatric Disorders
- Anorexia nervosa
- Intractable obsessive—compulsive disorder
- Severe, intractable and disabling anxiety.
- Medical Disorders
- Huntington's chorea
- Intractable hiccough
- Nausea and vomiting
- Tic disorder
- Heat stroke
- Severe pain in malignancy
The oral dose is absorbed erratically but with even blood level oral dose give peak level of 1½ hours, intramuscular administration gives more reliable blood level and peaks at 30 nots.
Since the antipsychotics are lipophilic, they easily enter into brain, kidneys, and lungs via blood. The dose is given based on the half-life drug.
The drugs are mainly metabolized in liver and excreted through kidneys. The effective/toxicity of the drug is based on the ‘therapeutic window’ of the drug.
- Antipsychotic when administered orally are absorbed variably from the gastrointestinal tract, with uneven blood levels.
- They are highly bound to plasma as well as tissue protein.
- Brain concentration is higher than plasma concentration.
- They are metabolized in liver, and excreted mainly through the kidneys. The elimination half-life varies from 10–24 hours.
- Most of the antipsychotic tend to have a therapeutic window. If the blood level is below this window, the drug is ineffective.
MECHANISM OF ACTION
- Antipsychotic drugs block D2-receptors in the mesolimbic and mesofrontal systems (concerned with motioned reactions).
- Sedation is caused by alpha-adrenergic blockade.
- Antidopaminergic actions on basal ganglia are responsible for causing EPS (extrapyramidal symptoms).
- Atypical antipsychotics have antiserotonergic (5-hydroxyl-tryptamine or 5-HT). Antiadrenergic and antihistaminergic actions. These are therefore called as serotonin-dopamine antagonists.
MODE OF ACTION
The mechanism of action of antipsychotics is unknown. But, most probably, one of the major mechanism is the antidopaminergic activity of these drugs.
Antipsychotic drugs block D2-receptors the dopamine receptors which are mainly present in the mesolimbic system (mesolimbic system is concerned with emotional reactions) and extrapyramidal system. The relative potencies of these drugs in competing for D2-receptors parallel quite closely their clinical potencies.
The neurotransmitters (e.g. 5-HT, acetylcholine) are clearly implicated. The newer antipsychotics (called as SPA agents or serotonin dopamine antagonists) like risperidone, particularly act on the 5-HT2 receptors.
Sedation is caused by histaminergic blockade, which is maximum for chlorpromazine and thioriodazine.
The antipsychotics, when administered to a psychotic patient, corrects this disordered thinking, difficulties in attention and concentration and perceptual abnormalities. In addition, the psychomotor activity becomes normal in both excited and withdrawn patients.
TYPICAL VS ATYPICAL COMPARISON
The atypical, second generation medications were marketed as offering greater efficacy in reducing psychotic symptoms while reducing side effects (and extrapyramidal symptoms in particular) than typical medications. These results showing these effects often lack robustness.
A study compared several atypical antipsychotics to an older typical antipsychotic perphenazine, among 1493 persons with schizophrenia. Perphenazine was chosen because of its lower potency and moderate side effect profile, the study found that only olanzapine outer performed perphenazine in the researchers principle outcome, the discontinuation rate. The apparent superior efficacy of olanzapine to the other drugs for greater reduction in psychopathology—Longer duration of successful treatment and lower rate of hospitalization for an exacerbation of schizophrenia. No other atypical studied (risperidone, quetiapine and ziprasodone) did better than the typical perphenazine on those measures. Olanzapine was associated with relatively severe metabolic effects; subject with olanzapine showed a major weight gain problem and increases in glucose, cholesterol and triglycerides, perphenazine did not create more extrapyramidal side effect, although more patients discontinued perphenazine owing to extrapyramidal effects compared to the atypical agents.
A subsequent phase was conducted dopamine indeed proved to be more effective at reducing medication drop-outs than other neuroleptic agents.
- Clozapine (Clozaril)—It requires weekly to biweekly CBC (FBC) because of risk of agranulocytosis (a severe decrease of white blood cells).
- Olanzapine (Zyprexa)—It is used to treat psychotic including schizophrenia, acute manic episodes and maintenance of bipolar disorder. Dosing 2.5 mg–20 mg per day, comes in a form that quickly dissolves in the mouth (Zyprexa zydis). It may cause appetite increase, weight gain and altered glucose metabolism leading to an increased risk of diabetes mellitus.
- Risperidone (Risperdal)—Dosing 0.25 mg–6 mg per day and is titrated upward; divided dosing is recommended until initial titration is completed at which time the drug can be administered once daily. Available in long-acting form (Risperdal consta that is administered every 2 weeks; usual dose is 25 mg) comes in a form that quickly dissolves in the mouth (Risperdal of Tab) used off label to treat Tourette syndrome.
- Quetiapine (Seroquel)—It is used primarily to treat bipolar disorder and schizophrenia, and ‘off label’ to treat chronic insomnia and restless legs syndrome; it is a powerful sedative (if it's used to treat sleep disorders and is not effective at 200 mg, it is not going to be effective in this regard).Dosing starts at 25 mg and continue upto 800 mg maximum per day, depending on the severity of the symptom(s)-being treated, users typically take smaller dose during the day for the neuroleptic properties and larger dose at bed time for the sedative effects, or divided in two equally high doses every 12 hours (75 mg – 400 mg bid).
- Ziprasidone (Geodon)—Now (2006) approved to treat bipolar disorder. Dosing 20 mg twice daily initially upto 80 mg twice daily, prolonged QT interval a concern; watch closely with patients who have heart disease; when used with other drugs that prolong QT interval potentially life-threatening.
- Amisulpride (Solian)—Selective dopamine antagonist, higher doses (greater than 400 mg) act upon postsynaptic dopamine receptors resulting in a reduction in the positive symptoms of schizophrenia, such as psychosis lower doses however act upon dopamine autoreceptors, resulting in increased dopamine transmission, improving the negative symptoms of schizophrenia.
- Paliperidone (Invega)—Derivative of risperidone. Approved in December, 2006.
Dopamine partial agonists—
- Aripiprazole (Abilify)—Dosing 5 mg upto maximum of 30 mg has been used. Mechanism of action is thought to reduce susceptibility to metabolic.
- Under clinical development—Bifeprunox, norclozapine.
|CLASSIFICATION AND PROPERTIES OF ANTIPSYCHOTICS TYPICAL ANTIPSYCHOTICS|
Class and E.g. of Drugs
E.g. of trade names
Oral dose range (mg/day)
Parental dose range (mg)
Equivalent dose (equal to sedation 100 mg of CPZ)
Side effects Hypotension
Eps (extrapyramidal symptoms)
50–100 mg IM only
25–50 IM Every 13 weeks
6.7 (for 25 mg is given every 2 weeks)
20–40 IM every 2–4 weeks
40 mg every 2 weeks = 25 mg decanoate every 2 wks
100 mg every 4 weeks = 5 mg/day of Haloperidol
20–60 mg once every week
3.5 Probably for 20 mg given every week
|SIDE EFFECTS OF ANTIPSYCHOTIC DRUGS|
Dry mouth, constipation, cycloplegia, mydriasis, urinary retention, central anticholinergic syndrome tachycardia, orthostatic hypotension, impotence impaired ejaculation.
Blockade of muscarine cholinergic receptor
Usually tolerance develops.
Otherwise treated with laxatives pilocarpine 2% diazepam, etc.
Parkinsonian syndrome (EPS tremor), akathisia (motor restlessness), acute dystonia, rabbit syndrome (perional tremor), tardive dyskinesia (oral facial), neuroleptic malignant syndrome.
Dopamine receptor Blockade
Seizure, sedative, depression, pseudodepression drowsiness, dizziness, lethargy, fatigue.
Adrenergic blockade, reduced catecholamine level
Decrease the dose, then continue
Weight gain, galactorrhea, amenorrhea, increased appetite, glycosuria
Dopaminergic blockade leads to prolactine secretion
Change of drugs
Cholestatic jaundice, agranulocytosis
Stop the drug
EKG changes, sudden death
Change the drugs
Granular deposit in cornea and in lens, pigmentary retinopathy, blurred vision.
Reduce the dose or change the drug
Contact dermatitis, photosensitive reaction, blue gray discoloration, pruritus, eczema, erythema
Reduce the dose or change the drug
Fever, muscle stiffness, decreased sweating, nasal congestion, pale skin
Reduce the dose or change the drug
Antipsychotics are contraindications in children under three years of age, comatose patients, patient with drug hypersensitivity, severe depression, and bone marrow depression.
- Nurses should be aware of the side effects of the antipsychotic drugs and observe for the same in the patients.
- If she observe early EPS symptoms, she should inform the doctor and injection phenergan may be given in severe form. For mild EPS tab. Pacitane 2 mg may be given.
- Maintain vital chart.
- For female, look for breast enlargement and maintain menstrual charting.
- Weekly weight record should be maintained.
- Watch for neuromalignant syndrome which is a serious problem.
- When patients are on a typical antipsychotics watch for agranulocytosis.
- Any infections should be recognized and taken care in time.
- Advise the patient to get up slowly from squatting lying down position.
Haloperidol is a typical antipsychotic, it is in the butyrophenone class of antipsychotic medications and has pharmacological effects similar to the phenothiazines.
Haloperidol is a primitive antipsychotic used in the treatment of schizophrenia and more acutely, in the treatment of acute psychotic states and delirium. A long-acting decanoate ester is used as a long-acting injection given every 4 weeks to people with schizophrenia or related illness who have a poor compliance with medication and suffer frequent relapses of illness.
It was developed in 1957 by the Belgian company Janssen Pharmaceutica and submitted to first clinical trials in Belgium in the same year.
Haloperidol is a neuroleptic and butyrophenone. Due to its strong control antidopaminergic action, it is classified as a highly potent neuroleptic. Haloperidol possesses a strong activity against delusions and hallucinations. Most likely due to an effective dopaminergic receptor blockage in the mesocortex and the limbic system of the brain. It blocks the dopaminergic action in the nigrostriatal pathways, which is the probable reason for the high frequency of extrapyramidal myotonic side effects (dystonia, akathisia, pseudoparkinsonism) it has minor antihistaminic and anticholinergic properties, therefore cardiovascular and anticholinergic side effects such as hypotension, dry mouth, constipation, etc. are seen quite infrequently, compared with less potent neuroleptics such as chlorpromazine. Haloperidol also has sedative properties and display a strong action against psychomotor agitation but due to a specific action in the limbic system it is therefore is an effective treatment for mania and states of agitation. Additionally it can be given as an adjuvant in the therapy of severe chronic pain.
The peripheral antidopaminergic effects of haloperidol account of its strong antiemetic activity. There it acts at the chemoreceptor trigger zone (CTZ). Haloperidol is useful to treat severe forms of nausea/emesis such as those resulting from chemotherapy.
The drug is well and rapidly absorbed and has a high bioavailability plasma levels reach their maximum within 20 minutes after injection.
The bioavailability is 100% and the very rapid onset of action is seen within about ten minutes, the duration of action is 3–6 hours. If haloperidol is given as slow IV infusion, the onset of action is retarded, but the duration prolonged compared to 1 mg injection.
Plasma levels of 4 micrograms per liter to 20 (upto 25) micrograms per liter are required for therapeutic action. The determination of plasma levels can be used to calculate dose adjustments and to check compliance, particularly in long-term patients.
Haloperidol has found it to be an effective agent in treatment of symptoms associated with schizophrenia. Haloperidol is also used in the control of the symptoms of—
- Acute psychosis, such as drug psychosis (LSD, amphetamines, ketamine and phencyclidine) psychosis associated with high fever or metabolic diseases.
- Acute manic phases until the concomitantly given firstline drugs such as lithium or valproate are effective.
- Hyperactivity, aggression.
- Acute delirium.
- Otherwise uncontrollable severe behavioral disorders in children and adolescents.
- Agitation and confusion associated with cerebral sclerosis.
- Adjunctive treatment of alcohol and opioid withdrawal.
- Treatment of neurological disorders such as tic disorder, Tourette syndrome and chorea.
- Treatment of severe nausea/emesis (postoperative, side effects of radiation and cancer chemotherapy).
- Adjunctive treatment of severe chronic pain, always together with analgesics.
- Therapeutic trial in personality disorders such as borderline personality disorders.
- Also used in the treatment of intractable hiccups.
- Pre-existing coma, acute stroke.
- Severe intoxication with alcohol or central depressant drugs.
- Known allergy against haloperidol or other butyrophenones or other drug ingredients.
- Known heart disease, when combined will tend towards cardiac arrest.
Special caution needed
- Pre-existing Parkinson's disease.
- Patients at special risk for the development of QT prolongation.
- Compromised liver function.
- Haloperidol may decrease the seizure—Threshold. Treat patients with epilepsy and those with risk factors for the development of seizures with caution. Maintain existing anticonvulsive therapy.
- Patients with hyperthyreosis; the action haloperidol is intensified and side effects are more likely, initiate an effective therapy of hyperthyreosis.
- IV injections: Inject slowly to avoid hypotension or orthostatic collapse. Avoid IV injections in cardiovascular unstable patients (preexisting hypotension, shock, concomitant antihypertensive therapy, heart insufficiency) prefer in these cases moderate oral or 1 mg doses.
The drug is noted for its strong early and late extrapyramidal side effects. The risk of the facial disfiguring tardive dyskinesia is around 4% per year in younger patients, higher than with most other antipsychotic drugs. Other predispositive factors may be female gender, pre-existing affective disorder and cerebral dysfunction.
Akathisia manifests itself with anxiety, dysphasia and an inability to remain motionless, other side effects include dry mouth lethargy, restlessness of akathisia, muscle-stiffness, muscle-cramping, restlessness, tremors and weight gain. Depression, severe enough to result in suicide is quite often seen during long-term treatment. Fatal neuroleptic malignant syndrome (NMD) is a significant possible side effect.
Pregnancy and Lactation
Unconfirmed studies is pregnant women revealed possible damage to the fetus, although most of the women were exposed to multiple drugs during pregnancy, following accepted general principles, haloperidol should only be given during pregnancy if the benefit to the mother clearly outweighs the potential fetal risk.
Haloperidol, when given to lactating women, is found to significant amounts in their milk. Breastfed children sometimes show extrapyramidal symptoms. If the use of haloperidol during lactation seems indicated, the benefit for the mother should clearly outweigh the risk for the child consider termination of breastfeeding.
So far, no statistically acceptable evidence is found to associate long-term use of haloperidol with the potential for increased breast cancer risk in female patients.
- Other central depressants (alcohol, tranquilizers, narcotics): Actions and side effects of these drugs.
- Methyldopa: Increased risk of extrapyramidal side effects and other unwanted central effects.
- Levodopa: Decreased action of levodopa.
- Tricyclic antidepressants: Metabolism and elimination of tricyclics significantly decreased, increased toxicity noted.
- Quinidine, buspirone and fluoxetine: Increased plasma levels of haloperidol, decrease haloperidol dose.
- Carbamazepine, phenobarbital and rifampicin.
As directed by the physician, depends on the condition to be treated, age and weight of patient.
Single doses of 1 mg – 5 mg (upto 10 mg) oral or, IM usually repeated every 4–8 hours. Do not exceed an oral dose of 100 mg daily. Doses used for IV injection are usually 5 mg – 10 mg as a single dose; not exceeding 50 mg daily.
0.5 mg – 20 mg daily oral, rarely more. The lowest dose that maintains remission should be employed.
In resistant cases of psychosis small studies with oral doses of upto 300 mg – 500 mg daily have been conducted to avoid severe early extrapyramidal side effects.
Symptoms are usually due to exaggerated side effect. Most often encountered are—
- Severe extrapyramidal side effects with muscle rigidity and tremors, akathisia, etc.
- Hypotension or hypertension.
- Anticholinergic side effects—Dry mouth, constipation, paralytic ileus, difficulties in urinating, massive sweating.
- Coma in severe cases, accompained by respiratory depression and massive hypotension, shock.
- Rarely serious ventricular arrhythmia.
- Epileptic seizures.
Treatment is merely symptomatic and involves intensive care with stabilization of vital functions. In early detected cases of oral overdose induction of emesis, gastric lavage and the use of activated charcol can all be tried. Avoid epinephrine for treatment of hypotension and shock because its action might be reversed.
Generally, the prognosis of overdose is good and lasting damage is not known, provided that the patient has survived the initial phase.
ADVERSE EFFECTS OF ANTIPSYCHOTIC DRUGS
- Extrapyramidal symptoms (EPS):These are the serious neurologic symptoms and major side effects of antipsychotic drugs.
- Neuroleptic-induced parkinsonism
- Rigidity, tremors
- Stooped posture
- Akinesia, ataxia.
- Acute dystonia
- Involuntary movement
- Restless and feel generally dysphonic.
- Tardive dyskinesia
- Irregular choreoathetotic movements of the muscles of the head, limb and trunk.
- Neuroleptic malignant syndrome
- Onset is often, but not invariably
- Motor hypertonicity
- Stiffness of the muscles in the throat and chest
- The mental symptoms are akinetic mutism stupor.
- Autonomic side effects:
- Dry mouth
- Urinary retention
- Orthostatic hypotension
- Impotence and impaired ejaculation.
- Other effects
- Agranulocytosis (especially for clozapine)
- Sialorrhea or increased calivation (especially for clozapine)
- Weight gain
- Dermatological effects (contact dermatitis, photosensitive reaction).
- Instruct the patient to take sips of water frequently to relieve dryness of mouth.
- A high-fiber, increased fluid intake and laxatives if needed help to reduce constipation.
- Check BP before and after medication is given.
- Differentiate between akathisia and agitation and inform the physician.
- Observe the patient regularly for abnormal movements.
- Take all seizure precautions.
- Patient should be warned about driving a care operating machinery.
- Advise the patient to use sunscreen measures for photosensitive reaction.
- Teach the importance of drug complications, side effect, and regular follow-up.
- Seizure precaution should taught. Clozapine reduces seizure threshold.
Antidepressants are those drugs which are used for the treatment of depressive illness. These are also called as mood elevators or thymoleptics. Antidepressants agents are used in affective disorders or disturbances mainly to treat depressive disorder caused by emotional and environmental stressors.
For example, tricyclic antidepressants (imipramine), tetracyclic antidepressants (maprotilene), monoamine oxidase inhibitors (isocarboxazid).
|CLASSIFICATION OF ANTIDEPRESSANTS|
Oral dosage mg/day
Tricyclic antidepressants (TCAS)
75 – 300
75 – 300
75 – 300
30 – 120
Selective serotonin reuptake
10 – 80
50 – 200
50 – 300
100 – 400
150 – 600
10 – 30
- Depressive episode
- Reactive depression
- Secondary depression
- Abnormal grief reaction.
- Childhood psychiatric disorders
- Separation anxiety disorder
- School phobia
- Night terrors.
- Other psychiatric disorders
- Panic attack
- Generalized anxiety disorder
- Agoraphobia and social phobia
- OCD with or without depression
- Eating disorder
- Borderline personality disorder
- Posttraumatic stress disorder
- Depersonalization syndrome.
- Medical disorders
- Chronic pain
- Peptic ulcer disease.
- Antidepressants are highly lipophilic and protein bound.
- The half-life is long and usually more than 24 hours it is predominantly metabolized in the liver.
Mechanism of Action
The exact mechanism is unknown. The predominant action is by increasing catecholamine levels in the brain.
- Autonomic side effects: Dry mouth, constipation, cycloplegia, mydriasis, urinary retention, orthostatic hypotension, impotence, impaired ejaculation, delirium.
- CNS effects: Sedation, tremor and other extrapyramidal syndrome, seizures, jitteriness syndrome, precipitation of mania.
- Cardiac side effects: Tachycardia, ECG changes, arrhythmias, direct myocardial depression.
- Allergic side effects: Agranulocytosis, cholestatic jaundice, skin rashes.
- Metabolic and endocrine side effects: Weight gain.
- Patients on MAOIs should be warned against the danger of ingesting tyramine-rich foods which can result in hypertensive crisis.(beef liver, chicken liver, fermented sausages, dried fish, overripe fruits, chocolate and beverage like—Wine, beer and coffee).
- Report promptly if occipital headache, nausea, vomiting, chest pain or other unusual symptoms occur, these can herald the onset of hypertensive crisis.
- Restrict the patient not to take any medication without prescription.
- Strict monitoring of vitals, especially blood pressure is essential.
Bipolar disorder is a common recurrent and often severe psychiatric illness associated with high rates of morbidity and mortality if left untreated. Bipolar disorder also called manic-depressive disorder. Bipolar refers to the experience of both poles of mood: Mania and depression.
It is important to develop a comprehensive treatment plan for the patient with bipolar disorder including individual, family and psychosocial therapies is a critical component. The mood stabilizers include lithium. Valproate, carbamazepine, and other anticonvulsant mood stabilizers in the treatment of bipolar disorders.
Mood stabilizers are used for the treatment of bipolar affective disorders. Some commonly used mood stabilizers are:
- Sodium valproate.
Antimanic drugs are a class of medicines used to treat mania or manic phase of the bipolar disorders. It has also been used in the treatment of manic-depressive and schizoaffective disorders.
The major use of an antimanic agent is for treatment of mania and recurrent manic episodes.
DESIRED TREATMENT OUTCOMES
- Eliminate the symptoms of the mood episodes
- Stabilize the mood to prevent cycling between depression and mania
- Improve the client's self-care ability, function and quality of life.
MODE OF ACTION
The specific biochemical mechanism of action of antimanic agents is unclear.
Antimanic agents produce many neurochemical changes in the area of brain. These changes may affect norepinephrine and serotonin in the part of CNS involved in emotion. It may decrease the activity of the nerve impulse, resulting in depression or increase in the nerve impulse, causing mania.
Lithium also helps in maintaining the sodium concentration in the brain, thereby regulating the mood servings as well as impulse along the nerve cells.
|CLINICAL AND PHARMACOKINETIC PARAMETERS OF MOOD STABILIZERS (ANTIMANIC AGENTS)|
Dosage range (mg/day)
Acute 1800 maintenance
400 – 1300
21 – 30
5 – 14 days
400 – 1300
300 – 500
1200 – 2500
5 – 20
1200 – 2500
5 – 20
TARGET SYMPTOMS FOR MOOD-STABILIZING DRUG THERAPY
Mania, irritability, euphoria, expansiveness, manipulativeness, lability with depression, sleep disturbance (decreased sleep), pressured speech, flight of ideas, motor hyperactivity, assualtiveness/threatening behavior, distractibility, hypergraphia, hypersexuality, persecutory and religious delusions, geandiosity hallucinations, ideas of reference, catatonia.
Lithium is a naturally occurring alkali metal that shows some characteristic with other monovalent cations such as sodium and potassium. In 1949, cade in Australia, was the first to report the therapeutic effects of lithium to treat mania.
Lithium is used to treat acute hypomanic or manic episodes and recurrent affective disorders. 70%–90% of client with typical bipolar illness respond to lithium.
Some times, lithium is used to treat schizoaffective disorders, often in conjunction with an antipsychotic agent. Lithium is been found to be effective in the treatment of aggressive or impulsive behaviors.
Lithium is an element with atomic number 3 and atomic weight 7. It was discovered by Fj Code in 1949, and is a most effective and commonly used drug in the treatment of mania.
Lithium salt used in treatment of a myriad of psychiatric and nonpsychiatric disorders—
- Rx of acute mania
- Prophylaxis of bipolar mood disorder
- Rx of schizoaffective disorder
- Rx of cyclothymia
- Rx of acute depression
- Chronic alcoholism
- Rx of impulsive aggression
- Rx of Kleine-Levin syndrome.
Other disorders are:
- Premenstrual dysphonic disorder
- Bulimia nervosa
- Borderline personality disorder.
Lithium is available in market in the form of the following preparations—
- Lithium carbonate 300 mg tab. 400 mg sustained release tablet.
- Lithium citrate 300 mg/5 ml liquid.
Before starting treatment, it is essential to make sure of normal functioning of kidneys thyroid, heart and CNS. After starting lithium it is necessary to investigate these systems at repeated intervals. Usual profile of investigation as follows:
- Routine general and systemic physical examination
- Routine blood counts (Hb, TC, DC, ESR)
- Urine-routine and microscopic examination
- Renal function tests (blood urea, serum creatinine, 24 hours urine volume, urine specific gravity). GFR with creatinine clearance test
- Thyroid function test.
Lithium is readily absorbed with peak plasma levels occurring 2 – 4 hours after a single oral dose of lithium carbonate. Lithium is distributed rapidly in liver and kidney and more slowly in muscle, brain and bone. Steady-state levels are achieved in about 7 days. Elimination is predominantly via kidneys. Lithium is reabsorbed in the proximal tubules and is influenced by sodium balance. Depletion of sodium can precipitate lithium toxicity.
Mechanism of action
The probable mechanisms of action can be—
- Accelerates presynaptic re-uptake and destruction of catecholamines, like norepinephrine.
- Inhibits the release of catecholamines at the synapse
- Decreases postsynaptic serotonin receptor sensitivity.
The following mechanisms of action of lithium have been hypothesized.
- If affects the Na+– K+– ATPase and accumulates intracellularly as a substitute of Na+.
- It inhibits the adenylate cyclase and thus decreases CAMP messenger intracellularly.
- It accelerates the presynaptic reuptake and destruction, of catecholamines like norepinephrine.
- It inhibits the release of catecholamines at the synapse.
- It decreases the postsynaptic serotonin 5HT2 receptor sensitivity.
- It stabilizes the cell membrane, along with Ca++ and Mg++.
- Decreases the Ca++ mobilization from the intracellular pools by inositol triphosphate dependent Ca++ channels.
- It interferes with the phosphatidy-inositol cycle by blocking the conversion of inositol monophosphate to inositol by inositol monoposphate phosphatase. The muscarinic acetylcholine (ACh) receptor is among one of the neurotransmitter receptors linked to this system in brain. The antimanic effects of lithium may be attributed to this effect on ACh, thus affecting cholinergic-adrenergic balance. All these actions result in decreasing catecholamine activity, thus ameliorating mania.
Lithium is available in the market in the form of the following preparations:
Lithium carbonate—300 mg tablets (lithcab), 400mg (lithoSUNSR)
Lithium citrate—300 mg/ 5 ml liquid.
Blood lithium levels
Therapeutic levels = 0.8–1.2 mEq/l (treatment for acute mania) Prophylactic levels = 0.6–1.2 mEq/l (prevention of relapse in bipolar disorder)
Toxic lithium levels >2.0mEq/l.
- Neurological: Tremors, motor hyperactivity, muscular weakness, seizures, and neurotoxicity (delirium, abnormal involuntary movement).
- Renal: Polydipsia, polyuria, tubular enlargement, and nephrotic syndrome.
- Cardiovascular : T-wave depression.
- Gastrointestinal: Nausea, vomiting, diarrhea, abdominal pain, and metallic taste.
- Endocrine: Abnormal thyroid function, goiter, and weight gain.
- Dermatological: Acneiform eruptions, popular eruptions, and exacerbation of psoriasis.
- Lithium toxicity: Toxicity occurs when serum lithium level > 2.0 mEq /l.
- Side effects during pregnancy and lactation:
- Increased incidence of Ebstein's anomaly
- Secreted in milk with 30% – 100% of maternal blood lithium levels can cause toxicity in infant.
Signs and symptoms of lithium toxicity
- Coarse tremor (hand)
- Nausea and vomiting
- Impaired memory
- Impaired concentration
- Muscle weakness
- Muscle twitching
|ADVERSE EFFECTS ASSOCIATED WITH LITHIUM THERAPY|
Plasma level (mEq/l)
Common side effects
Less common side effects
Initial Rx: fine hand tremors, polyurea, mild thirst, transcent and mild nausea and discomfort Afterwards: fatigue, acne, ECG changes, hypothyroidism
Twitching, muscular weakness restlessness dry mouth and thinning hair
1.5 – 2.0
Diarrhea, vomiting, nausea drowsiness, muscle weakness, lack of coordination
2.0 – 3.0
Giddiness, ataxia, blurred vision, tinnitus, vertigo, increased confusion, slurred speech blackout, incontinence fasciculation, myoclonic
Seizures, arrhythmias, hypotension, peripheral vascular collapse, stupor, spasticity
Contraindications of lithium use
- Cardiac, renal, thyroid or neurological dysfunction
- Presence of blood dyscrasias
- During first trimester of pregnancy and lactation
- Severe dehydration
- History of seizures
- Presence of clear evidence of cardiac, renal thyroid or neurological dysfunction
- Presence of blood dyscrasia
- During first trimester of pregnancy and lactation
- Concomitant administration of thiazide, diuretics, tetracyclines or anesthetics.
Management of lithium toxicity
- Discontinue the drug immediately.
- For significant short-term ingestions, residual gastric content should be removed by induction of emesis, gastric lavage, and absorbtion with activated charcoal.
- If possible instruct the patient to ingest fluids.
- Assess serum lithium levels, serum electrolytes, renal functions, and ECG as soon as possible.
- Maintenance of fluid and electrolyte balance.
- In a patient with serious manifestations of lithium toxicity, and hemodialysis should be initiated.
The prelithium work-up
A complete physical history, ECG, blood studies (TC, DC, FBS, BUN, creatinine, electrolyte), and urine examination (routine/micro) must be carried out. It is important to assess renal function as renal side effects are common and the drug can be dangerous in an individual with compromised kidney function.
To achieve therapeutic effect and prevent lithium toxicity, the following precautions should be taken
- Lithium must be taken on a regular basis, preferably at the same time daily (a patient taking lithium on TID schedule, who forgets a dose should wait until the next scheduled time to take lithium and not take twice the amount at one time as it can lead to lithium toxicity).
- When lithium therapy is initiates mild side effects such as find hand tremors, increased thirst and urination, nausea, and anorexia, may develop.
- Serious side effects of lithium that necessitate its discontinuance.
- Since polyuria can lead to dehydration with the risk of lithium intoxication, patient should be advised to drink enough water to compensate for the fluid loss.
- Frequent serum lithium level evaluation is important.
- Blood for determination of lithium level should be drawn in the morning approximately 12–14 hours after the last dose was taken.
- The patient should be told about the importance of regular follow-up.
Carbamazepine is an antimanic and mood-stabilizing agent. It is a tricyclic compound synthesized in 1953 by Schindler.
The onset of action is faster as compared to lithium, but slower compared to valproate 600 mg – 1600 mg/day orally is divided dose Rx is best monitored with repeated blood levels. The therapeutic blood levels are 6 mg – 12 mg/ml. The toxic blood levels are reached at more than 15 mg/ml.
It is available in the market under different tradenames like tegretol, mazetol, zeptol and zen retard.
- Seizures— Complex partial seizures, GTCS, seizures due to alcohol withdrawal.
- Psychiatric disorders— Rapid cycling bipolar disorder, acute depression, aggression, psychosis with epilepsy, schizo-affective disorders, personality disorder, cocaine withdrawal syndrome.
- Paroxysmal pain syndromes— Trigeminal neuralgia and phantom limb pain.
The average daily dose is 600 mg – 1800 mg orally, in divided doses.
The therapeutic blood levels are 6 mg – 12 mg/ml. Toxic blood levels are attained at more than 15 mg/ml.
Mechanism of action
It is structurally related to imipramine. It enhances GABA activity in the brain and inhibits glutamate and aspartate activity. It possesses psychotropic effects and is less sedating thorn most anticonvulsants. The drug elevate mood in some depressed client and is a second line Rx for bipolar disorder.
Its mood-stabilizing mechanism is not clearly established. It anticonvulsant action may however be by decreasing synaptic transmission in the CNS.
Major: Diplopia, drowsiness, dizziness, nausea, vomiting, ataxia, skin rash, photosensitivity, cholestatic jaundice, acute oliguria with hypertension, leukopenia, and thrombocytopenic purpura.
Most dangerous side effects: Bone marrow depression Cardiovascular collapse.
It is essential to monitor cardiac, renal, hepatic, and bone marrow functions during treatment.
Avoid during pregnancy and lactation.
- Skin rashes
- Nausea and vomiting, diarrhea
- Dry mouth
- Abdominal pain
- Since the drug may cause dizziness and drowsiness advise him to avoid driving and other activities requiring alertness.
- Advise patient not to consume alcohol when he is on the drug.
- Emphasize the importance of regular follow-up visits and periodic examination of blood count and monitoring of cardiac, renal, hepatic and bone marrow functions.
SODIUM VALPROATE, ENCORATE, CHRONO, VALPARIN, EPILEX, EPIVAL
Effective as carbamazepine in the treatment of bipolar disorder. It should be considered an alternative for clients unable to tolerate carbamazepine.
Mechanism of action
Oxcarbazepine is the 10-keto, 11-dihydro-co-ox-carbazepine analog of carbamazepine.
- Headache, drowsiness, dizziness, and ataxia
- Tremor, abnormal gait, fatigue, and sedation encephalopathy
- Hyperlipidemia, antidiuretic hormone effective allied reproductive hormones.
Used in bipolar depression and in rapid cycling bipolar disorders.
Lamotrifine requires a slow titration; the titration schedule must be followed to minimize risk of skin rash.
- GI distress
- Blurred or double vision.
- Interactions with valproate.
Gabapentin (Neurontin) is a GABA analog. Gabapentin has been used for adjunctive therapy as a mood stabilizer and for the treatment of partial seizure in social phobia.
Gabapentin has many other uses including adjunctive therapy in alcohol detoxification, anxiety disorder, dystonia, essential tremor OC behavior, phantom limb syndrome, and pain management.
Absorption, distribution, metabolism and execution
The bioavailability of gabapentin decreased with increasing dose. Its bioavailability is approx 60% when dosed at 400 mg every 8 hours.
Bioavailability is reduced to 35% at a does of 1200 mg every 8 hours.
Less than 35% of gabapentin is protein bound drug is not metabolized but executed unchanged in wine.
- Hypertension, vasodilation, edema, peripheral edema, and facial edema
- Fluctuations in blood sugar levels
- Ataxia, dizziness, involuntary movements, somnolence, and pruritic rash.
Topiramate is a sulfamate substituted monosaccharide and indicated for treatment of epilepsy.
Topiramate is also used in the treatment of binge eating, bulimia, cluster headache, and trigeminal neuralgia.
Absorption, distribution, metabolism and execution
- It is well-absorbed after oral doses peak serum concentration occur in 2–4 hours
- Food alters the rate of absorption
- Topiramate is minimally bound to protein
- Druff is not metabolized and is executed unchanged in urine.
It should be treated slowly, initial dose of 50 mg/day, for 1st week and increased in 50 mg increments per week until a dose of 400 mg/day is reached.
- Hypertension, postural hypotension, vasodilation arrhythmias, and palpitations
- Drowsiness, dizziness, ataxia, speech disorders, confusion, language problems, and anxiety
- Auditory hallucination.
Nurse's responsibility when patients are on antimanic drugs
- Before lithium therapy. Excessive weight gain or swelling of ankles and wrists should be noted weekly weight record should be maintained.
- Regular serum lithium level LFT (liver function test) and Rx (thyroid function test) to be monitored.
- Monitor Na intake.
- Above 40 years ECG to be done regularly.
- Stop the drug if fluid loss occurs and then restart.
- Activities which increases perspiration.
- Careful monitoring of blood count to be done and any kind of infection to be notified early.
- Advice the patient not to increase or decrease medicine unless advised.
Anxiolytics (Antianxiety Drugs)
These are also called as minor tranquilizers. Most of them belong to the benzodiazepine group of drugs.
- Nonbarbiturate, nonbenzodiazepine, and antianxiety agents:
- Benzodiazepines: Presently benzodiazepines are the drugs of first choice in the treatment of anxiety, and for the treatment of insomnia.
- Very short-acting :
–Oxazepam (Serepax)–Lorazepam (Ativan, Trapex, Larpose)–Alprazolam(Restyl, Trika, Alzolam, Quiet)
–Chlordiazepoxide (Librium)–Diazepam (Valium, calmpose)–Clonazepam (Lonazep)–Flurazepam (Nindral)–Nitrazepam (Dormin).
Indications for Benzodiazepines
- Anxiety disorders
- Panic disorder and social phobia
- Obsessive compulsive disorder
- Posttraumatic stress disorder
- Bipolar-I disorder
- Other psychiatric indications include alcohol withdrawal, substance-induced and psychotic agitation.
Dosage (mg/ day)
- Alprazolam 0.5 – 6 mg/day PO
- Oxazepam 15 – 120 PO
- Lorazepam 2 – 6 PO/IV/IM
- Diazepam 2 – 10 PO /IM/ slow IV
- Clonazepam 0.5 – 20 PO/IM
- Chlordiazepoxide 15 – 100 PO, 50 – 100 slow IV
- Nitrazepam 5 – 20 PO.
Mechanism of Action
Benzodiazepines bind to specific sites on the GABA receptors and increase GABA level. Since GABA is an inhibitory neurotransmitter, it has a calming effects on the central nervous system, thus reducing anxiety.
- Nausea, vomiting, and weakness
- Vertigo, and blurring of vision
- Bodyaches, epigastric pain, and diarrhea
- Impotence, and sedation
- Increased reaction time
- Ataxia, dry mouth, and retrograde amnesia
- Impairment of driving skills
- Dependence and withdrawal symptoms.
- Administer with food to minimize gastric irritation.
- Advise the patient to take medication exactly as directed. Abrupt withdrawal may cause insomnia, irritability and sometimes even seizures.
- Explain about adverse effects and advise him to avoid activities that require alertness.
- Caution the patient to avoid alcohol or any other CNS depressants along with benzodiazepines.
- If IM administration is preferred give deep IM.
- For IV administration do not mix with any other drugs. Give slow IV as respiratory or cardiac arrest can occur: Monitor vital signs during IV administration.
Sedatives and Hypnotics
It is rapidly emerging as a first line drug for treatment of mania.
Valproic acid was first synthesized by Burton and used as organic solvent. It was approved by US FDA as an antiepileptic drug for absence seizures in 1978 and for the treatment of acute mania in 1996.
The term valproate is often used to denote all commercial preparations since the common entity in blood is valproic acid.
- Valproate sodium
- Chrono preparation.
- Acute mania, prophylactic treatment of bipolar-I disorder, rapid cycling bipolar disorder.
- Schizoaffective disorder
- Other disorders like bulimia, nervosa, obsessive-compulsive disorder, agitation and PTSD.
- Acute Mania (as a first line agent for Rx of acute mania in oral and IV forms) several factors associated with a favorable antimanic response to valproate (as well as carbamazepine).
- Comorbid substance abuse.
- Late age of onset and shorter duration of illness.
- History of poor response to lithium dysphoric mania, mixed affective episodes, and rapid cycling.
- Organic/complicated mania associated with seizure disorder, and head trauma.
- D–M–I (Depression-Mania–Well Interval).
- Prophylaxis valproate is less effective in the maintenance treatment of bipolar disorder than in treatment of acute mania. It has been used alone as well as long with lithium and other mood stabilizers in maintenance treatment.
- Rapid cycling bipolar disorders and mixed/dysphoric mania: Patients with rapid cycling mixed affective episodes or dysphoric mania are often resistant to lithium treatment and respond better to valproate.
- Bipolar depression: Valproate appears to be more effective in the Rx of acute mania than in depression.
- Migraine and pain syndrome: Valproate has been used for the prophylaxis of migraine headaches, as well as for aborting an acute attack also used in trigeminal neuralgia and neuropathic pain.
- Seizure disorder: Valproate is primarily indicated for Rx of absence seizures, complex partial seizures, myoclonic seizures generalized tonic-clonic seizures.
Also been used in behavioral afitation in dementia, severe behaviroal symptoms in mental retardation, schizoaffective disorder, alcohol withdrawal, tardive dyskinesia, impulse control disorder, and panic disorder.
Nausea, sedation, tremor, flushing, weight gain, thrombocytopenia, menstrual disturbance (in women), and hair loss. There are some reports of polycystic ovaries and hyperandrogenism in young women with epilepsy.
Serious side effect are hepatic toxicity acute hemorrhagic pancreatitis. Use of valproate in pregnancy and lactation should be avoided.
Certain drug may increase (e.g. Aspirin, cimetidine ibuprofen, erythromycin, and fluoxitine) or decrease (carbamazepine, phenytoin, phenobarbital refampicin) the serum levels of valproate, valproate increase levels of other drugs (e.g. Lamoteifine, and tricyclic antidepressants).
MECHANISM OF ACTION
The drug acts on gamma-aminobutyric acid [GABA] an inhibitory amino acid neurotransmitter. GABA receptor activation serves to reduce neuronal excitability.
The usual dose is 15 mg/kg/day with a maximum of 60 mg/kg/day orally.
- Nausea, vomiting, and diarrhea.
- Sedation, ataxia, dysarthria, tremor, weight gain, and loss of hair.
Thrombocytopenia, and platelet dysfunction.
Nausea, sedation, tremor, flushing, weight gain, thrombocytopenia, menstrual disturbance (in women), and hair loss. There are some reports of polycystic ovaries and hyperandrogenism in young women with epilepsy.
Serious side effects are hepatic toxicity and acute hemorrhagic pancreatitis. Use of valproate in pregnancy and lactation should be avoided.
- Advise the patient to take the drug immediately after food to reduce GI irritation.
- Advise regular follow-up, and periodic examination of blood count, hepatic function and thyroid function.
- Therapeutic serum level of valproic acid is 50 mg – 100 mg/ml.
In clinical practice anticholinergic drugs, amitadine and the antihistamines have their primary use as treatments for medication-induced movement disorders, particularly neuroleptic-induced parkinsonism, acute dystonia, and medication-induced tremor.
Monoamine Oxidase Type B inhibitors–
- SelegilineTrihexyphenidyl (Artane, trihexane, trihexy, and pacitane).
- Drug-induced parkinsonism
- Adjunct in the management of parkinsonism.
MECHANISM OF ACTION
It acts by increasing the release of dopamine from presynaptic vesicles, blocking the reuptake of dopamine into presynaptic nerve terminals or by exerting an agonist defect on postsynaptic dopamine receptors. Trihexyphenidyl reaches peak plasma concentrations in 2–3 hours after oral administration and has duration of action upto 12 hours.
1 mg – 2 mg per day orally initially, maximum dose upto 15 mg/day in divided doses.
- Dizziness, and nervousness
- Drowsiness, weakness, and headache
- Confusion, and blurred vision
- Mydriasis, and tachycardia
- Orthostatic hypotension
- Dry mouth, nausea, and constipation
- Urinary retention and decreased sweating.
- Assess parkinsonism and extrapyramidal symptoms.
- Medication should be tapered gradually.
- Caution, patient to make position changes slowly to minimize orthostatic hypotension.
- Instruct the patient about frequent rinsing of mouth and good oral hygiene.
- Caution, the patient when this medication decreases, perspiration, and overheating may occur during hot weather.
Disulfiram is an important drug in this class and is used to ensure abstinence in the treatment of alcohol dependence. Its main effect is to produce a rapid and violently unpleasant reaction in a person who ingests even a small amount of alcohol while taking disulfiram.
Antabuse has been used since 1951 to help people stop drinking (the generic name of antabuse is Disulfiram). Antabuse is not only effective for stopping drinking. If you have a drug problem, anything that helps you stop drinking will also help you stop using drugs, because alcohol usually leads to drugs.
Antabuse works by making you sick to your stomach if you have a drink. It works because if you know you can't drink, then you won't think about drinking as much.
Numerous studies have proven that antabuse is effective. It has been shown to reduce cravings for alcohol and to reduce the risk of relapse. It has also proven to reduce the risk of relapse in adolescent addicts.
People who use antabuse feel liberated. That internal struggle that goes on everyday, ‘Will I drink? Won't I drink?’ Is silenced when you're on antabuse. Because drinking is not an option you don't waste your time thinking about drinking, and instead you focus more on your recovery.
Antabuse is effective, because you have to wait for one to two weeks before you can have a drink after you stop antabuse. You can't stop antabuse one day and have a drink the next. It gives you plenty of time to reconsider, restart your antabuse, and ask for help.
Antabuse is a bridge between your two lives. On the one hand, you have the life that you know. It's not what's good for you, but it's what you know. On the other hand, you have the life that you want to get to. It's better for you, but you don't know how to live there. You don't know how to relax, reward yourself, and celebrate without using drugs or alcohol. Antabuse helps you live in that lifelong enough, so that you can develop new habits and coping skills.
Antabuse, or disulfiram as it is also known, was the first medicine approved for the treatment of alcohol abuse and alcohol-dependence by the US. Food and Drug Administration.
Antabuse is prescribed to help people who want to quit drinking by causing a negative reaction if the person drinks while they are taking antabuse.
MECHANISM OF ACTION
When alcohol is consumed it is metabolized by the body into acetaldehyde, a very toxic substance that causes many hangover symptoms heavy drinkers experience. Usually, the body continues to oxidize acetaldehyde into acetic acid, which is harmless.
Antabuse interferes with this metabolic process, stops the process with the production of acetaldehyde and prevents the oxidation of acetaldehyde into acetic acid. Because of this, antabuse will cause a build up of acetaldehyde 5 or 10 times greater than normally occurs when someone drinks alcohol.
It takes one drink to produce a reaction. It takes one bottle of beer, one glass of wine, or one shot of liquor to become sick.
The normal sequence of the antabuse reaction is—
- Flushing of the face
- Low blood pressure
- Racing heart
- Nausea and vomiting.
If you have one drink, you will vomit about as much as if you had food poisoning.
A few people are very sensitive to antabuse and get a stronger reaction. A quick test of whether you're sensitive to antabuse is to see if your skin flushes when you put alcohol on your skin. If you're sensitive, you may still decide to use antabuse, but you'll have to be a little more careful about avoiding alcohol. Most people just need to show some common sense when they're on antabuse.
EFFECT OF ANTABUSE
The high concentration of acetaldehyde that occurs when someone drinks while taking antabuse can cause reactions that range widely from mild to severe, depending on how much antabuse and how much alcohol is consumed, none of which are pleasant.
If you drink while taking antabuse, you can experience these symptoms:
- Copious vomiting
- Throbbing in the head and neck
- Throbbing headache
- Respiratory difficulty
- Chest pain
- Marked uneasiness
- Blurred vision
Those are the ‘mild’ symptoms. Severe reactions can include respiratory depression, cardiovascular collapse, myocardial infarction, acute congestive heart failure, unconsciousness, arrhythmias, convulsions, and death.
USE OF ANTABUSE
Only someone who wants to try to quit drinking and who is fully aware of the consequences of drinking while on the medication should take antabuse. Antabuse should never be given to some without their full knowledge or to anyone who is intoxicated.
Because of the possible severe reactions, antabuse should not be given to anyone with a history of severe heart disease, psychosis, or an allergy to antabuse. Women who are pregnant should not take antabuse and no one taking paraldehyde or metronidazole should use antabuse.
ANTABUSE DOES NOT DO
Antabuse serves merely as physical and psychological deterrent to someone trying to stop drinking. It does not reduce the person's craving for alcohol, nor does it treat any alcohol withdrawal symptoms.
DO'S AND DON'TS OF ANTABUSE
Wait at least 24 hours after drinking before starting antabuse. Consider the following arithmetic. If you had 10 drinks and weighed only 100 Ibs (45 kg), the alcohol would be completely eliminated from your system in 24 hours. If you weighed more than 100 Ibs (45 kg) it would take less than 24 hours.
For most people, it takes one drink to produce an antabuse reaction, therefore it's hard to get by mistake. You can have foods that have been cooked in wine, as long as they've been cooked the alcohol evaporates quickly. You have to be careful of some deserts that have a lot of uncooked alcohol in them. You also have to be careful of some cough syrups and cold preparations that can contain as much as 40% alcohol.
Most people prefer to use nonalcoholic mouthwashes to be on the safe side. Although the amount of alcohol you absorb from mouthwash does'nt equal one drink, assuming you don't drink your mouthwash.
You can use perfumes, colognes, or aftershaves. The amount of alcohol you absorb through your skin is minimal.
The standard patient information sheet on antabuse says that you should avoid all of these things: Mouthwash, perfumes, colognes, even vinegar. But I've treated thousands of patients, and I've never known any of them to get a reaction from anything other than drinking. Antabuse liberates you, if you use a little common sense.
EFFECTIVENESS OF ANTABUSE
The effectiveness of antabuse in helping someone quit drinking depends on the person's continued use of medication. Because antabuse is administered in a daily pill, people can merely stop taking the drug and begin drinking a few days later.
However, research in Europe, where antabuse is much more widely used than in the United States, has shown that long-term use of antabuse is very effective in helping people stop drinking, producing abstinence rates of 50 percent. The longer people take antabuse, the more effective it is, because they develop a ‘habit’ of not drinking, research revealed.
The side effects of antabuse are less common than the side effects of relapse. During the first week or two that you take antabuse, you'll probably feel a little more tired. It usually lasts for a week or two and then it goes away.
During the first two months that people take antabuse, about 20% develop a funny taste in their mouth. It's usually decribed as a metallic taste. Eighty percent of people don't get it, and if you do get that taste, it often goes away after a few weeks or months. That's it for the minor side effects of antabuse.
The major side effects of antabuse are rare. The most common but still rare side effect of antabuse is liver damage. Any drug that you take over a long-term has the potential to cause liver damage. With antabuse, it happens in roughly one out of 30,000 people.
Your doctor can do a simple blood test to check the state of your liver before you start. After you've been on antabuse for a month you should have your liver tests repeated. Your doctor should periodically check your liver enzymes while you're on antabuse.
Any drug can have any possible side effect. You can never say never in medicine. Every year people die from taking tylenol (acetaminophen). But that doesn't mean we should stop using tylenol. The benefits far outweigh the risks. And the benefits of antabuse outweigh the risks of drinking.
Before taking antabuse you should give your doctor your entire medical history. You may not be able to take antabuse if you have a significant medical history of heart or blood vessel disease, diabetes, and underactive thyroid, brain disorders (e.g. seizures, brain damage), kidney disease, liver disease, a history of severe depression, a history of psychosis, or a history of suicide attempts. Antabuse can alter the metabolism and blood levels of certain drugs, especially tricyclic antidepressants, Dilantin (phenytoin), coumadin, isoniazid, and theophyline.
Do not take antabuse if you're pregnant, or trying to become pregnant.
SERIOUS WARNING SIGNS
If you notice any of the following rare but serious warning signs, stop using antabuse and tell your doctor immediately: Dark urine, severe abdominal pain, presistent nausea or vomiting, and yellowing of the eyes or skin.
RESISTANCE TO TRYING ANTABUSE
There are only three reasons why you may be reluctant to try antabuse.
First, because you're worried about the side effects. Although the side effects of antabuse can be serious, they are rare. The side effects of relapsing on alcohol are common and serious.
The second reason is because you want to do your recovery on your own. You've always been self-reliant and you want to be self-reliant in your recovery. But recovery involves learning to ask for help. Doing it on your own is overrated. You need to ask for help from your doctor, treatment program, 12 step group, and sponsor. Antabuse is just one more thing you can use. It is not an alternative to your supports. It complements them.
The third and final reason why you may be reluctant to try antabuse is because you want to leave the door open to having a drink. Just in case you want to relapse there won't be anything in your way. Of course, if you leave that door open then it's guaranteed you'll relapse eventually. It's just a matter of time.
If you've decided that you want to change your life. If you've decided that you have suffered enough negative consequences, then I encourage you to talk to your doctor about antabuse.
GETTING A PRESCRIPTION
Speak to your doctor about antabuse. Antabuse is available at most pharmacies, and is a simple drug that can be made by most pharmacists. If you are a Canadian resident and your doctor cannot find a pharmacy that dispenses antabuse, it can be ordered through www.pharmacy.ca, which is an internet pharmacy that delivers free of charge through Canada Post.
There are three antialcohol drugs available:
- Antabuse (disulfiram)
- Campral (acamprosate)
- Revia (naltrexone).
I have focused on antabuse for a few reasons. It has a long track record, and is considered safe and effective. Its available in generic form, which means that it's quite inexpensive. The cost of antabuse is a lot less than the price of alcohol.
Studies have shown that antabuse is at least as effective, and sometime more effective than the other two medications, which have only been around for a few years 5–6 years.
A RECOVERY CHECKLIST
A list of important goals for the first year of your recovery. Use it as a reminder and to help you stay on track in the days and months ahead.
- Accept that you have and addiction
- Practice honesty in your life
- Learn to avoid high-risk situations
- Ask for help
- Practice calling friends before you have cravings
- Become actively involved in self-help recovery groups
- Go to discussion meetings and begin to share
- Get a sponsor and do step work
- Get rid of using friends
- Make time for you and your recovery
- Celebrate your small victories. Recovery is about progress not perfection
- Practice saying no
- Take better care of yourself
- Develop healthy eating and sleeping habits
- Learn to relax and let go of stress
- Discover how to have fun, clean and sober
- Make new recovery friends and bring them into your life
- ‘Play the tape forward’ to deal with cravings
- Find ways to distract yourself when you have cravings
- Deal with postacute withdrawal symptoms
- Develop a strategy for social settings where drinking is involved
- Thank the supportive people in your life
- Develop tolerance and compassion for yourself and others
- Say goodbye to your addiction
- See yourself as a nonuser.
HELP FOR THE FAMILY
An addiction destroys families as much as it destroys individuals. Living with an addict is both heartbreaking and exhausting. Family members are torn between how to help the addict and how to avoid being sucked into the addict's world.
Here are some helpful suggestions that I have found over the years of working with addicts and their families. I hope they can help you.
THINGS YOU CAN DO FOR THE ADDICT
- Behave exactly as you would if your loved one had a serious illness. What would you do if they were diagnosed with heart disease or cancer?
- Educate yourself on addiction and recovery.
- Try not to accuse or judge. Avoid name calling. This is a difficult time for both of you.
- Provide a sober environment that reduces triggers for using.
- Allow the addict time to go to meetings.
- Understand that your lives will change. Do not wish for your old life back. Your old life to some extent is what got you here. You both need to create a new life where it is easier to not use alcohol or drugs.
- Make sure that you both have time for fun. People use alcohol and drugs to relax, escape, and as a reward. The addict needs to find alternative ways to relax, escape, and as a reward otherwise they will turn back to their addiction.
- Do not enable. Do not provide excuse or cover up for the addict.
- Do not shield the addict from the consequences of their addiction. People are more likely to change if they have suffered enough negative consequences.
- Set boundaries that you all agree on. The goal of boundaries is to improve the health of the family as a whole. Do not use boundaries to punish or shame.
- If you want to provide financial support, buy the goods and services the addict needs instead of giving them money that they might use to buy alcohol or drugs.
- Recognize and acknowledge the potential the addict has within them.
THINGS YOU CAN DO FOR YOURSELF
- Take care of yourself. Living with an addict is exausting. You also need time to recover.
- Avoid self-blame. You can't control another person's decisions, and you can't force them to change.
- Do not work harder than the addict. The best approach is not to do things for the addict, but instead to be an example of balance and self-care.
- Being a caretaker is not good for you or the addict. Understand that there is only so much you can do to change another person.
- Ask for help. Talk to professional. Go to a support group such as Al-Anon. (More support groups are listed below).
- Do not argue or try to discuss things with the addict when they are under the influence. It won't get you anywhere.
- If at all possible, try not to be negative when dealing with the addict. That may only increase their feelings of guilt and push them further into using.
THE THREE C'S OF DEALING WITH AN ADDICT
- You didn't cause the addiction
- You can't control the addiction
- You can't cure the addiction.
‘You can't stop drinking or using for another person’.
HELPFUL LINKS FOR FAMILY AND FRIENDS OF ADDICTS
- Nar-anon (nar-anon.org) for family members of addicts
- Gam-anon (gam-anon.org) for family members of gamblers
12 STEP GROUPS
- Alcoholics Anonymous (AA) (aa.org)
- Adult Children of Alcoholics (ACA)(adultchild.org)
- All-Addictions Anonymous (alladdictionsanonymous.com)
- Cocaine Anonymous (CA) (ca.org)
- Crystal Meth Anonymous (CMA) (crystameth.org)
- Dual Recovery Anonymous (UK): A 12-setp Program for those with a dual diagnosis
- Food Addicts in Recovery Anonymous (FA) (foodaddicts.org)
- Gamblers Anonymous (GA) (gamblersanonymous.org)
- Narcotics Anonymous (NA) (na.org)
- Nar-Anon (nar-anon.org) for family members of addicts
- Nicotine Anonymous (nicotine-anonymous.org)
- Marijuana Anonymous (marijuana-anonymous.org)
- Methadone Anonymous (methadoneanonymous.info)
- S-Anon (sanon.org)
- Sex and Love Addicts Anonymous (SLAA) (slaafws.org)
- Women for Sobriety (WFS) (womenforsobriety.org)
- XA Speakers (xa-speakers.org) A collection of recordings from speaker meetings, conventions and workshops of 12-step groups.
- 12 Steps (12step.org) Resources for all 12 step programs. It contains an in-depth discussion and forum on the 12 steps.
- 12StepTreatmentCenters.com A list of 12 Step treatment centers around the world.
- National Institute of Alcohol Abuse and Alcoholism (niaaa.nih.gov)
- National Institute of Drug Abuse (nida.nih.gov)
- National Clearinghous for Alcohol and Drug Information (ncadi.samhsa.gov)
- Substance Abuse and Mental Health Services Administration (samhsa.gov)
- National Institute of Mental Health (nimh.nih.gov)
- Smoke Free (smokefree.gov)
- World Health Organization.
- Addiction Recovery Guide Addiction and recovery resources
- American Lung Association (lungusa.org)
- American Society of Addiction Medicine (asam.org)
- Benzodiazepine Addiction, Withdrawal and Recovery (benzo.org.uk)
- Canadian Addiction, Counsellors Certification Federation (caccf.ca). An organization that certifies and monitors addiction counselors in Canada.
- Canadian Lung Association (lung.ca)
- Canadian Society of Addiction Medicine (csam.org)
- Employee Assistance Professionals Association (eapassn.org)
- Employee Assistance Program Association of Toronto (eapat.org)
- Helping Others Live Sober Aimed at people in recovery and professionals. Together, we are united in the shared goal of Helping Others Live Sober.
- International Center for Alcohol Policies (icap.org)
- National Association of Alcoholism and Drug Abuse Counselors (NAADAC) (naadac.org) An organization that certifies and monitors addiction counselors.
- Partnership for Drug Free America(drugfree.org)
- Project Cork (projectcork.org).
- Alcohol Rehab
- Benzo Withdrawal Forums Online group for benzodiazepine addiction, withdrawal and recovery.(benzowithdrawal.org)
- Crossorads (Antigua)
- Drug and Alcohol Treatment Referral
- Food Addiction
- Metamorphosis Clinic
- My Addiction
- Overcoming Addiction
- Pressing The Issue
- Stop And Think Radio
- Recovery Connection
- Support Groups
- Valley Hope: Drug and alcohol rehab nonprofit organization.
Answer the following seven yes or no questions. Most questions have more than one part, because everyone behaves differently in addiction. You only need to answer yes to one part for that question to count as a positive response.
- Tolerance: Has your use of drugs or alcohol increased over time?
- Withdrawal: When you stop using, have you ever experienced physical or emotional withdrawal? Have you had any of the following symptoms: Irritability, anxiety, shakes, sweats, nausea, or vomiting?
- Difficulty controlling your use: Do you sometimes use more or for a longer time than you would like? Do you sometimes drink to get drunk? Do you stop after a few drink usually, or does one drink lead to more drinks?
- Negative consequences: Have you continued to use even though there have been negative consequences to your mood, self-esteem, health, job, or family?
- Putting off or neglecting activities: Have you ever put off or reduced social, recreational, work, or household activities because of your use?
- Spending significant time or emotional energy: Have you spent a significant amount of time obtaining, using, concealing, planning, or recovering from your use? Have you spend a lot of time thinking about using? Have you ever concealed or minimized your use? Have you ever thought of schemes to avoid getting caught?
- Desire to cut down: Have you sometimes thought about cutting down or controlling your use? Have you ever made unsuccessful attempts to cut down or control your use?If you answered yes to at least 3 of these questions, then you meet the medical criteria (DSM and ICD) for addiction.There are no restrictions on the printing of this document. It is provided as a public service by www.AddictionAndRecovery.org. For a more complete guide to addiction refer to the book ‘I Want to Change My Life’ by Dr. Steven M. Melemis.
Answer the following 10 yes or no questions. Most questions have more than one part, because everyone feels their depression differently. You need to answer yes to only one part per question in order for that question to count.
- Depressed mood: Do you feel sad, down, or depressed most of the time? Do you feel that all the color has been drained out of your life? Do you cry more easily? Do you have crying spells for no apparent reason?
- Loss of interest: Have you lost interest in things that used to give you enjoyment? Have you lost interest or enjoyment in the activities of daily life? Are you more socially withdrawn or isolated?
- Low energy: Is your energy lower? Do you feel more fatigued or sluggish? Is it hard to get going in the morning? Is your libido suddenly reduced or do you have less interest in sex?
- Anxiety or irritability: Are you more anxious, worried, fearful, irritable, or intolerant?
- Lower self-confidence: Is your self-confidence or self-esteem lower? Do you feel more hopeless or pessimistic? Do you feel more guilty or worthless?
- Poor concentration: Is it hard for you to think, concentrate, or make decisions? Do you find it hard to concentrate outside of work? Do you find it harder to read articles or to take in what you read?
- Sleep changes: Do you have difficulty falling asleep or staying asleep? On the weekends do you feel like you could sleep all day and don't want to get out of bed? Do you feel that you're not refreshed when you wake up in the morning?
- Appetite or weight change: Is your appetite either significantly lower or higher than a year ago? Have you unintentionally lost or gained weight? Do you eat only because you have to eat, but don't get any pleasure from food?
- Slow moving or restless: Are you more slow moving lately? Is your speech slower lately? Do you feel like you're shuffling when you walk? Are you restless or fidgety? Do you wring your hands more?
- Thoughts of death: Do you have recurrent thoughts of death or suicide (not just a fear of dying)? Do you think it would be easier if you just didn't wake up in the morning? Do you think it would be easier if you developed a serious illness? Do you wonder if anyone will miss you when you're gone? Do you think you would be better off dead, or that your family would be better off if you were gone? Do you imagine ways of hurting yourself?
If you answered yes to at least 5 of these questions, then you meet the medical criteria (DSM and lCD) for depression.
There are no restrictions on the printing of this document. It is provided as a public service by www.AnxietyDepressionHealth.org. For a more complete guide to depression refer to the book ‘I Want to Change My Life’ by Dr. Steven M. Melemis.
Drugs Used in Child Psychiatry
Control of withdrawal symptoms from opioids
- Tourette's disorders
- Control of aggressive or hyperactive behavior in children
Mechanism of Action
- Alpha 2- adrenergic receptor agonist
- The agonist effects of clonidine on presynaptic alpha 2-adrenergic receptors result in a decrease in the amount of neurotransmitter released from the presynaptic nerve terminal.
Usual starting dosage is 0.1 mg orally twice a day: The dosage can be raised by 0.3 mg a day to an appropriate level.
- Dry mouth, dryness of eyes, and fatigue
- Irritability and sedation
- Dizziness, nausea, and vomiting
- Hypotension and constipation.
- Monitor BP, the drug should be withheld if the patient becomes hypotensive.
- Advise frequent mouth rinses and good oral hygiene for dry mouth.
Methylphenidate, dextroamphetamine and pemoline are sympathomimetics.
- Attention–deficit hyperactivity disorder
- Depressive disorders
Mechanism of Action
- Sympathomimetics cause the stimulation of alpha and beta-adrenergic receptors directly as agonists and indirectly by stimulating the release of dopamine and norepinephrine from presynaptic terminals.
- Dextroamphetamine and methylphenidate are also inhibitors of catecholamine reuptake, especially dopamine reuptake and inhibitors of monoamino oxidase. The next result of these activities is believed to be the stimulation of several brain regions.
Starting dose is 5 mg – 10 mg per day orally, maximum daily dose is 80 mg/day.
- Anorexia or dyspepsia
- Weight loss, slowed growth
- Insomnia or nightmares
- Dysphoric mood, tics and psychosis.
- Assess mental status for change in mood, level of activity, degree of stimulation, and aggressiveness.
- Ensure that patient is protected from injury.
- Keep stimuli low and environment as quick as possible to discourage overstimulation.
- To decrease anorexia, the medication may be administered immediately after meal.
- The patient should be weighted regularly during hospitalization.
- To prevent insomnia administer last dose at least 6 hours before bedtime.
- In children with behavior disorders a drug ‘holiday’ should be attempted periodically under the direction of the physician to determine effectiveness of the medication and the need for continuation.
- Ensure that parents are aware of the delayed effects of Ritalin. Therapeutic response may not be seen for 2–4 weeks, the drugs should not be discontinued for lack of immediate results.
- Inform patients that OTC (over-the-counter) medications should be avoided while the child is on stimulant medication.
- Some OTC medications, particularly cold and hay fever preparations contain certain sympathomimetic agents that could compound the effect of the stimulant and create drug interactions that may be toxic to the child.
- Ensure that parents are aware that the drug should not be withdrawn abrupt.
- Sreevani R. A Guide to Mental Health and Psychiatric Nursing; 3rd ed. Jaypee Brothers Medical Publishers(P) Ltd: New Delhi. 2009; 93 – 106.