Antipsychotic drugs indications

When administering the antipsychotic drugs, the nurse observes the patient for extrapyramidal effects , which include muscular spasms of the face and neck, the inability to steep or s t still, tremors rigidity, or involuntary rhythmic movements The nurse notifiesthe primary health care provider of the occurrence of these symptoms because they may indicate a need for dosage adjustment. 

It is common for lithium to be combined with other mood-stabilizing drugs or antipsychotic drugs, if necessary, in order to achieve more complete remission of symptoms. Studies indicate that monotherapy is often insufficient to reach this goal.17... 

Introduced in clinical practice in the 1960s, lithium was the first mood stabilizer to be used in China. This was followed by carbamazepine and sodium valproate. For many years, these were the only treatment options available as mood stabilizers. Although lamotrigine was approved for maintenance treatment of bipolar I disorder in 2003 by FDA (Food and Drug Administration) in the USA, this indication has not yet been approved by the Chinese authorities. At present, only one atypical antipsychotic drug, risperidone, has been approved for treating acute mania (February 2005 by SFDA [State Food and Drug Administration]) in China (see Table 6.1). 

FIGURE 58-7 The IC50 values (ordinate) are the concentrations of the antipsychotic drugs that reduce the stereospecific component of 3H-haloperidol binding by 50%. The abscissa indicates the average values (and ranges) of doses used for schizophrenia. (From Seeman, P. et al. Antipsychotic drug doses and neuroleptic/dopamine receptors. Nature 261 717-719,1976)... 

Acetazolamide is a carbonic anhydrase inhibitor that reduces aqueous humour production and is therefore indicated in glaucoma to reduce the intraocular pressure. Salbutamol is a selective, short-acting beta2-agonist used as a bronchodilator in asthma. Tolbutamide is a short-acting sulphonylurea used in type 2 (non-insulin dependent) diabetes mellitus. Chlorpromazine is an aliphatic neuroleptic antipsychotic drug used in schizophrenia. Zafirlukast is a leukotriene-receptor antagonist that is indicated in the prophylaxis of asthma but should not be used to relieve acute severe asthma. 

Largactil is a proprietary preparation of chlorpromazine, an aliphatic antipsychotic with marked sedation and moderate antimuscarinic and extrapyramidal side-effects. Serenace is a proprietary preparation of haloperidol, a butyrophenone antipsychotic with marked extrapyramidal side-effects, moderate sedation but not very likely to cause hypotension. Tegretol is a proprietary preparation of carbamazepine, an anti-epileptic drug indicated in partial and secondary generalised tonic-clonic seizures, primary generalised tonic-clonic seizures, trigeminal neuralgia and in the prophylaxis of bipolar disorder unresponsive to lithium. 

Antipsychotic drugs, such as flupentixol and haloperidol are the mainstay of treatment for acute attacks of mania. Lithium is not indicated as it may take a few days before the drug exerts an effect. Lithium may be given concomitantly with an antipsychotic drug. 

There are some indications that GABAergic axonal innervation is diminished in the cortex in schizophrenia. A deficit of GAD-immunoreactive puncta was reported in frontal cortex (Woo et al., 1998) and hippocampus (Todtenkopf Benes, 1998), while the cortical plexus of (GABAergic) parvalbumin-immunoreactive fibres is also diminished (Reynolds et al., 2001). The latter two studies reported a positive correlation of these measures of innervation with total antipsychotic drug exposure, indicative of protective or stimulatory effects of chronic drug treatment. 

Indications include a wide variety of psychiatric disorders, in the first place schizophrenia, organic psychoses and other acute psychotic illnesses. However they are also of use for the manic phase of bipolar affective disorder and for psychotic depression. Under antipsychotic drug therapy patients become less agitated and restless, withdrawn and autistic patients may become more communicative, aggressive and impulsive behavior diminishes and hallucinations and disordered thinking disappear. 

Antipsychotic drugs are characterized by high therapeutic indices with respect to mortality, but side effects occur routinely at therapeutic doses, mostly as exten-... 

The most common indications for antipsychotic drugs are the treatment of acute psychosis and the maintenance of remission of psychotic symptoms in patients with schizophrenia. More recently, the atypical antipsychotics have become part of the standard repertoire for the treatment of bipolar disorder, as discussed in Chapter 5. Antipsychotic drugs also ameliorate psychotic symptoms associated... 

The 2004 Practice Guideline for the Treatment of Patients With Schizophrenia recommends indefinite maintenance treatment for patients who have had at least two episodes of psychosis within 5 years or who have had multiple previous episodes (Lehman et al. 2004). Maintenance therapy should involve the lowest possible doses of antipsychotic drugs, and patients should be monitored closely for symptoms of relapse. If the patient is compliant with treatment, oral medications are usually sufficient. However, if the patient s treatment history suggests that the patient may not reliably take daily oral medication, a long-acting depot preparation may be indicated. 

Furthermore, clinical trials are performed in various cultural and geographical settings. Transcultural differences may play a significant role in drug efficacy e.g. oriental populations require much lower doses of antipsychotic drugs compared with Caucasian patient populations. Phase IV trials also may be performed to explore possible novel uses for compounds approved and marketed in other indications (e.g. treatment of anxiety disorders with antidepressants, treatment of bipolar disorder with anticonvulsants, etc.). 

As noted above, OC failure may lead to accidental pregnancy and exposure of the developing fetus to potentially teratogenic properties of CBZ ( 383). Therefore, OC levels should be closely monitored and patients should notify their physician of spotting, an indicator of OC failure. Prothrombin time and the International Normalized Ratio (INR) should be monitored when patients are on warfarin and CBZ concomitantly. Patients stabilized on an antipsychotic may decompensate when CBZ is added. This may necessitate an increase in the antipsychotic dose and is one indication for TDM of antipsychotic drug levels ( 384). Conversely, when CBZ is discontinued, the dose of these other agents may need to be lowered to avoid toxicity. In summary ... 

Nausea and sometimes vomiting may occur because of activation of 5-HT3 receptors. Tolerance generally develops to this within 7-10 days. A syndrome of agitation, which seems identical to the akathisia sometimes induced by antipsychotic drugs, may occur early in treatment in a small proportion of patients and is usually an indication to stop the SSRI. 

Most antipsychotic drugs cause unpleasant subjective effects in nonpsychotic individuals. The mild to severe EPS, including akathisia, sleepiness, restlessness, and autonomic effects are unlike any associated with more familiar sedatives or hypnotics. Nevertheless, low doses of some of these drugs, particularly quetiapine, are used to promote sleep onset and maintenance, although there is no approved indication for such usage. 

Schizophrenia is the primary indication for antipsychotic agents. Antipsychotic drugs are also used very extensively in patients with psychotic bipolar disorder (BP1), psychotic depression, and treatment resistant depression. 

Antipsychotic drugs are also indicated for schizoaffective disorders, which share characteristics of both schizophrenia and affective disorders. No fundamental difference between these two diagnoses has been reliably demonstrated. They are part of a continuum with bipolar psychotic disorder. The psychotic aspects of the illness require treatment with antipsychotic drugs, which may be used with other drugs such as antidepressants, lithium, or valproic acid. The manic phase in bipolar affective disorder often requires treatment with antipsychotic agents, although lithium or valproic acid supplemented with high-potency benzodiazepines (eg, lorazepam or clonazepam) may suffice in milder cases. Recent controlled trials support the efficacy of monotherapy with atypical antipsychotics in the acute phase (up to 4 weeks) of mania, and olanzapine and quetiapine has been approved for this indication. 

Other indications for the use of antipsychotics include Tourette s syndrome, disturbed behavior in patients with Alzheimer s disease, and, with antidepressants, psychotic depression. Antipsychotics are not indicated for the treatment of various withdrawal syndromes, eg, opioid withdrawal. In small doses, antipsychotic drugs have been promoted (wrongly) for the relief of anxiety associated with minor emotional disorders. The antianxiety sedatives (see Chapter 22) are preferred in terms of both safety and acceptability to patients. 

Until recently, lithium carbonate was the universally preferred treatment for bipolar disorder, especially in the manic phase. With the approval of valproate, aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone for this indication, a smaller percentage of bipolar patients now receive lithium. This trend is reinforced by the slow onset of action of lithium, which has often been supplemented with concurrent use of antipsychotic drugs or potent benzodiazepines in severely manic patients. The overall success rate for achieving remission from the manic phase of bipolar disorder can be as high as 80% but lower among patients who require hospitalization. A similar situation applies to maintenance treatment, which is about 60% effective overall but less in severely ill patients. These considerations have led to increased use of combined treatment in severe cases. After mania is controlled, the antipsychotic drug may be stopped and benzodiazepines and lithium continued as maintenance therapy. 

Consequently, antipsychotic drugs all share a basic mechanism of action that involves dopamine receptor blockade. It is apparent, however, that they are not all equal in their ability to affect specific sub-types of dopamine receptors, and that their effectiveness and side effects are related to their affinity and preference for certain receptors. As indicated earlier, other neurotransmitters may also be involved in the pathogenesis of psychosis, and differences in specific antipsychotic medications may be related to their ability to directly or indirectly affect these other transmitters as well as block dopamine influence. Future studies will continue to clarify how current antipsychotics exert their beneficial effects and how new agents can be developed to be more selective in their effects on dopamine and other neurotransmitter pathways. 

Most antipsychotic drugs have effects on the heart as a consequence of their pharmacological actions. Recently, thioridazine has been subjected to a restricted indication notice and the atypical antipsychotic sertindole had its licence withdrawn because of concerns about its potential cardiotoxicity. 

---