Here is an essay on the ‘Drugs Used for the Treatment of Mental Illness’ for class 11 and 12. Find paragraphs, long and short essays on ‘Drugs Used for the Treatment of Mental Illness’ especially written for college and medical students.
Essay # 1. Antipsychotic Drugs:
Psychosis may be defined as any major mental disorder of organic or emotional origin marked by derangement of personality and loss of contact with reality, delusions and hallucinations, often with incoherent speech, disorganized and agitated behavior or illness.
Major psychotic disorders include paranoia (delusional behavior), schizophrenia (mental disorders characterized by disturbances in the form and contents of thought, in mood, in sense of self and relationship to the external world and in behavior), and biopolar disorders or manic depressive disorders (characterized by marked swings in mood from depressive episodes to manic episodes).
Antipsychotic drugs (also known as major tranquillizers) are also called neuroleptics and are classified into two major groups classical or typical older antipsychotic drugs and atypical or new generation antipsychotic drugs. This classification is based on their mode of action, which accounts for fewer side effects on the motor system such as tremors and the usefulness in resistant cases of new generation antipsychotic drugs.
Mechanism of Action:
All antipsychotic drugs act by blocking dopamine D2 receptors in the brain. The older antipsychotic drugs possess broad-spectrum dopamine receptor-blocking properties, affecting all receptor subtypes and blockade of dopaminergic nerves that run from the substantia nigra to the corpus striatum which causes Parkinsonism. The new generation antipsychotic drugs have variable effects on dopamine receptor subtypes and on other neurochemical systems, such as serotonin.
A. Typical Antipsychotic Drugs:
The typical antipsychotic (neuroleptic) drugs are largely drawn from four distinct chemical groups:
a. The phenothiazines (for example, chlorpromazine);
b. The butyrophenones (haloperidol);
c. The thioxanthenes (for example, flupenthixol);
d. Other neuroleptics.
Chlorpromazine, the oldest phenothiazine, is still widely used despite the wide range of adverse effects associated with it.
Phenothiazines are erratically absorbed, are protein bound and enter the fetal circulation. Their biological effects last for 24 hours. Phenothiazines are largely metabolized by the hepatic microsomal system.
i. CNS effects:
Phenothiazines relieve florid psychotic symptoms such as thought disorders, hallucinations and delusions. The neuroleptic effects of antipsychotic drugs consist of emotional quietening, reduced physical movements with a little effect on intellectual functioning of the patient.
Most phenothiazine’s are potent anti-emetics; antagonize the action of apomorphine which stimulates the CTZ. In higher doses they may directly depress the medullary vomiting centre.
Phenothiazines alter temperature regulating mechanism and may cause dangerous hypothermia in the elderly.
Phenothiazine’s block all dopamine receptors and give rise to extrapyramidal effects and galactorrhoea. Weight gain and increase appetite are seen with phenothiazine use.
ii. Peripheral effects:
Anticholinergic, α adrenergic blocking activity and antihistaminic effects are seen. Chlopromazine is a potent local anesthetic. Orthostatic hypotension can occur as a result of central action as well as adrenergic blocking action. The most commonly used phenothiazines are given in Table 3.3.
Phenothiazines are used in schizophrenia and in other psychiatry conditions like psychosis, mania, short term adjunctive treatment of severe anxiety, psychomotor agitation, excitement and violent or dangerously impulsive behavior. They are in addition used as antiemetics, in the control of intractable hiccup, in severe pruritis and for induction of hypothermia in association with anesthetic drugs.
Phenothiazines commonly give rise to side effects, incidence of which varies with individual drug.
i. CNS effects:
Various disorders of movement are common due to dopamine blocking action, which includes Parkinson-like syndrome, akathisia (feeling of restlessness and inability to stand still), dystonia (uncontrolled movements especially of facial muscles and torticollis) and tardive dyskinesia (abnormal movements of the mouth and tongue and sometimes the upper limbs).
ii. CVS effects:
Orthostatic hypotension may cause syncope and reflex tachycardia.
iii. Allergic reactions:
Cholestatic jaundice, leucopenia and skin rashes may occur.
iv. Miscellaneous effects:
Dry mouth, weight gain, gynaecomastia, and rarely neuroleptic malignant syndrome with hyperpyrexia, coma and muscular rigidity may occur.
Benperidol, droperidol and haloperidol are the butyrophenones antipsychotics which are less sedating and have fewer anticholinergic or hypotensive actions, but are liable to produce more marked extrapyramidal (Parkinsonism-like) side effects than chlorpromazine. These drugs are mainly indicated for emergency control of schizophrenia and other psychosis.
Benperidol is indicated for the control of deviant antisocial sexual behavior. Droperidol is indicated for emergency control of mania. It is also used to control cancer chemotherapy induced nausea and vomiting. Haloperidol is indicated in schizophrenia and mania, short term management of violent or dangerously impulsive behavior and intractable hiccup. Butyrophenones rarely cause weight gain and are best avoided in basal ganglia disease.
Thioxanthines are similar to phenothiazines. They are useful antipsychotic and anti-emetics and are largely used in schizophrenia. Flupentixol is less sedating but extrapyramidal symptoms are more frequent. It should not be used in senile confusional states, excitable and overactive patients.
d. Other neuroleptics:
Pimozide is used in schizophrenia and manic states. It is long acting and less sedative than chlorpromazine, but can cause dangerous cardiac arrhythmias. Sulpiride has a more specific dopamine-blocking action than the other neuroleptics but with less adverse effects, though it may cause various disorders of movement and hepatitis.
B. Atypical Antipsychotic Drugs:
Atypical antipsychotic drugs differ from older neuroleptics in that they are better tolerated, extra-pyramidal symptoms and prolactin elevation may be less frequent. They block dopamine receptors more effectively in the areas of brain which are believed to be concerned with schizophrenia (the mesolimbic system). In addition they also block serotonin and adreno-receptors. The result is that they seldom cause disorders of posture and movements and may be effective when older neuroleptics fail.
Risperidone causes blockade of D2 as well as serotonin receptors. It has fewer extrapyramidal side effects and may be more broadly effective for the negative symptoms of schizophrenia compared with traditional antipsychotic drugs.
Clozapine possesses anticholinergic and serotonin-blocking properties. It produces proportionally greater suppression of mesolimbic as opposed to striatal dopamine systems. Clozapine blocks D2 receptors, as do other antipsychotic drugs, but it produces a relatively greater blockade of D1 systems, which may account for its altered pattern of efficacy and the absence of tardive dyskinesia as a side effect. Clozapine can cause fatal agranulocytosis which is not dose related and is reserved for patients not responding to other antipsychotic drugs.
Olanzapine blocks serotonin receptors in addition to a spectrum of dopamine receptors, including D1’ D2, and D4. It has also some anticholinergic and α1 blocking properties. This spectrum of pharmacologic properties generates fewer extrapyramidal side effects. It does not depress leucocyte count.
Quetiapine has actions and uses similar to clozapine. It is associated with a lower incidence of agranulocytosis. It may cause cataracts.
Ziprasidone is a new antipsychotic drug that favourably affects positive and negative symptoms of schizophrenia. It has low rates of extrapyramidal side effects but can cause akathisia. At present, it is impossible to say which is the best drug in this group, but they appear to offer advantages over the classical or typical neuroleptics.
Essay # 2. Antidepressant Drugs:
Depression, when disproportionate to precipitating factors (domestic and social conditions) or in absence of any obvious cause is an illness called endogenous or psychotic depression. Reactive depression or depressive neurosis is a type of depressive illness in which environmental factors play a more important role. Bipolar depression or maniac-depressive psychosis is characterized by depression which alternates with attacks of mania.
In depression the mood is at its lowest in the morning, the patient is disinterested and may be irritable and anxious and the appetite is poor. Suicide is a special risk in depressed patients. Antidepressant treatment should usually be considered only after detailed consideration of the nature of symptoms and causes.
Brain neurotransmitters and depression:
The aetiology of depression is not known but evidence suggests that a reduction in the amount of neurotransmitter amines such as noradrenaline or serotonin at the junctions between neurons in the brain is a major factor in causing depressive symptoms. Many antidepressant drugs act predominantly by inhibiting the reuptake of noradrenaline and serotonin into neurons, leading to an increase in the amount of these amines at the nerve receptors and their stimulation, which causes relief of depression.
Groups of antidepressant drugs:
a. Tricyclic antidepressants
b. Tricyclic anxiolytics
c. Selective serotonin re-uptake inhibitors
d. Other antidepressants.
e. Monoamine oxidase (MAO) inhibitors.
A. Tricyclic Antidepressant:
The tricyclic antidepressants do not differ significantly in their efficacy and the choice depends mainly on their sedative properties and incidence of side effects.
Commonly used tricyclic antidepressants are given in Table 3.4.:
Being highly lipid soluble, they are well absorbed from gut and metabolized in the liver. Some of the metabolites are therapeutically active.
In non-depressed persons there are no effect on the normal mood. The patient experiences sleepiness, anxiety, difficulty in concentrating and the effects are in general unpleasant. In depressed persons they are very effective and an elevation of mood occurs after a latent period of 2 to 4 weeks. Tricyclic antidepressants can cause extra-pyramidal symptoms and high doses may even result in convulsions and coma.
These constitute mainly side effects. Orthostatic hypotension and arrhythmias are most common. Atropine like effects is also common.
Tricyclic antidepressants are considered to be the drugs of choice for severe endogenous depression associated with sleep disorders. Amitriptyline, imipramine and nortryptiline are used for nocturnal enuresis in children. Clomipramine is the drug of choice in obsessive compulsive disorder resistant to treatment.
Atropine like side effects namely dry mouth, difficulty in micturition and constipation are common. They may cause postural hypotension, arrhythmias and heart block, increased appetite and weight gain, and increased tendency to seizures in patients with epilepsy. They are contraindicated in recent myocardial infarction, arrhythmias, manic phase and severe liver disease.
Analgesics (nefopam) and anti-epileptics increase the risk of convulsions. Anesthetics, antiarrhythmics, antipsychotics, and β blockers increase the risk of ventricular arrhythmia. MAO inhibitors increase CNS excitation and cause hypertension.
B. Tricyclic Anxiolytics:
These drugs have a weaker antidepressant action and a greater sedative action and are particularly useful when anxiety complicates mild depression. Their onset of action is more rapid than the standard tricyclics. Doxepin, dosulepin and maprotiline are commonly used. Side effects are similar to the tricyclics but are generally less marked. Maprotiline is more cardiotoxic.
C. Selective Serotonin Re-Uptake Inhibitors (SSRI):
SSRIs are an important advancement in antidepressant pharmacology because they are more specific in their neurochemical actions on the CNS than other drugs. They constitute the initial therapy for depressive illness. They block the reuptake of serotonin at presynaptic membranes, with relatively little effects on noradrenergic, cholinergic, histaminergic or other neurochemical systems. As a result, they are associated with a fewer side effects than the tricyclic antidepressants.
Their advantage lies in the lack of many of the adverse effects of the older tricyclics:
a. They are generally not cardio-toxic and therefore less dangerous in overdose
b. They do not cause hypotension
c. They do not give rise to atropine like actions
d. They do not cause weight gain.
Fluoxetine, fluvoxamine, sertaline, paroxetine, bupropion, citalopram and escitalopram are the ones available for use.
SSRI may replace tricyclics in depressive illness and obsessive compulsive disorders, because they are safe even in overdose. However, they should be used with caution in patients of epilepsy, history of mania, cardiac disease and hepatic and renal impairment.
GIT disorders (nausea and diarrhea), weight loss, headache and insomnia are fairly common. Hypersensitivity reactions may occur and suicidal ideas have been linked with fluoxetine. SSRI should not be used if the patient enters a manic phase.
MAO inhibitors or lithium, if combined, can cause serotonin like syndrome (hyperthermia, coma and fits), SSRIs increase the plasma concentrations of antipsychotics, benzodiazepines and propranolol.
D. Other Antidepressants:
There are several other antidepressants such as trazodone, venlafaxine, mirtazepine and bupropion which act by increasing the concentrations of noradrenaline and serotonin in the brain and are effective in depressive illness. They rarely offer any special advantage.
E. Monoamine Oxidase Inhibitors (MAOIs):
These are much less used because of dietary and drug interactions. Phenelzine, isocarboxazid and moclobemide are MAOIs that are commonly used. The main use of MAOIs is in atypical depression and phobic anxiety states.
Postural hypotension, insomnia, dizziness, GIT disorders, difficulty in micturition, psychotic episodes and rarely jaundice have been reported.
Sympathomimetics and tyramine containing food items such as cheese, meat, yeast extracts, some wines and beer, etc. may cause headache, hypertension, restlessness and even coma and death.
The body treats lithium in a similar way to sodium.
Mechanism of action:
Lithium is believed to act by modifying neurotransmission in the brain. It prevents the re-entry of catecholamines in the nerve endings in the brain and thus nerve receptors are stimulated leading to relief of depression. It also increases the rate of 5-HT synthesis in the brain; which is also concerned with the mood.
Lithium is well absorbed and eliminated by renal excretion. It is a very safe drug and its safety and efficacy depends on monitoring its blood levels. Lithium should not be prescribed if facilities for monitoring the blood concentrations are not available.
Lithium is the drug of choice for treatment and prophylaxis of mania, bipolar depression, recurrent depression and aggressive or self-mutilating behavior. Lithium has a low therapeutic index, i.e., blood levels above therapeutic levels are dangerous and can be fatal.
The common side effects are thirst, GIT disturbances, and fine tremors of hand, polyuria, muscular weakness and fatigue. Serious toxic reactions include toxic psychosis, convulsions, circulatory failure and coma. Dose unrelated toxicity is thyroid deficiency and weight gain. Lithium toxicity mimics barbiturate intoxication and requires good supportive care and excellent hydration. The only contraindication to lithium therapy is seriously compromised renal functions.
ACE inhibitors, NSAIDs and diuretics reduce lithium excretion. Antipsychotic, anti-epileptics, antihypertensive and calcium channel blockers increase the risk of neurotoxicity.