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 second-generation antipsychotics in the acute phase (up to 4 weeks) of mania. In addition, several second-generation antipsychotics are approved in the maintenance treatment of bipolar disorder. They appear more effective in preventing mania than in preventing depression. As mania subsides, the antipsychotic drug may be withdrawn, although maintenance treatment with atypical anti-psychotic agents has become more common. Nonmanic excited states may also be managed by antipsychotics, often in combination with benzodiazepines.
An increasingly common use of antipsychotics is in the mono-therapy of acute bipolar depression and the adjunctive use of antipsychotics with antidepressants in the treatment of unipolar depression. Several antipsychotics are now approved by the US Food and Drug Administration (FDA) in the management of bipolar depression including quetiapine, lurasidone, and olanzapine (in a combination formulation with fluoxetine). The antipsychotics appear more consistently effective than antidepressants in the treatment of bipolar depression and also do not increase the risk of inducing mania or increasing the frequency of bipolar cycling. Likewise, several antipsychotics, including aripiprazole, quetiapine, brexpiprazole, and olanzapine (with fluoxetine), are now approved in the adjunctive treatment of unipolar depression. Although many drugs are combined with antidepressants in the adjunctive treatment of major depression, antipsychotic agents are the only class of agents that have been formally evaluated for FDA approval for this purpose. Residual symptoms and partial remission are common, with antipschotics showing consistent benefit in improving overall antidepressant response.
Some of the intramuscular antipsychotics have been approved for the control of agitation associated with bipolar disorder and schizophrenia. Antipsychotics such as haloperidol have long been used in the ICU setting to manage agitation in delirious and postsurgical patients. The intramuscular forms of ziprasidone, olanzapine, and aripiprazole have been shown to improve agitation within 1–2 hours, with fewer extrapyramidal symptoms than typical agents such as haloperidol.
Other indications for the use of antipsychotics include Tourette syndrome and possibly disturbed behavior in patients with Alzheimer’s disease. However, controlled trials of antipsychotics in the management of behavioral symptoms in dementia patients have generally not demonstrated efficacy. Furthermore, second-generation as well as some first-generation antipsychotics have been associated with increased mortality in these patients. 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.
Psychotic symptoms associated with Parkinson’s disease represent a clinical challenge. Medications such as levodopa that treat the symptoms of Parkinson’s disease can also exacerbate psychotic symptoms. Likewise, antipsychotics that can treat the psychotic symptoms can significantly worsen the other symptoms of Parkinson’s disease. In 2016, a new type of antipsychotic was approved for the treatment of psychosis in Parkinson’s disease. Pimavanserin is a selective serotonin inverse agonist. As such, it has no dopamine antagonist properties and is not associated with EPS. Pimavanserin is currently being investigated as an adjunctive treatment in schizophrenia.
B. Nonpsychiatric Indications