Can Atypical Antipsychotics Reduce Suicide Risk in Patients With Schizophrenia?

Recommendations to use atypical antipsychotics for the treatment of depressive symptoms are complicated because most of them (except clozapine(Drug information on clozapine)) can potentially induce mania, an effect that has not been reported for typical antipsychotics.³¹ This phenomenon seems to be particularly relevant for ziprasidone(Drug information on ziprasidone),³¹ which, curiously, can also induce depression in patients with schizophrenia.³² This paradoxical finding is not unique to ziprasidone among the atypical antipsychotics, since depression associated with quetiapine(Drug information on quetiapine) has also been reported in patients with schizophrenia.³³

Active psychosis
Some patients with schizophrenia attempt and/or complete suicide in response to psychotic experiences.^34,35 The strongest evidence among these symptoms resides in command auditory hallucinations.²⁸

With the possible exception of clozapine, atypical antipsychotics are usually believed to have similar effectiveness in treating the positive symptoms of schizophrenia.³⁶

Agitation-hostility
Agitation and motor restlessness have been linked to suicidal behaviors.²⁸ A recent study by McGirr and Turecki³⁷ used the psychological autopsy method to examine 527 consecutive suicides, 43 of whom met criteria for schizophrenia and schizoaffective disorder. Elevated levels of impulsive-aggressive personality traits, considered an indicator of an elevated risk of suicide in other diagnostic categories, were found in these patients.

The effect of atypical antipsychotics on improving agitation states and hostility may be used to reduce the risk of suicidal behavior. Again, the strongest level of evidence lies with clozapine. A double-blind, randomized clinical trial has demonstrated the relative advantage of clo- zapine over other antipsychotics (at least haloperidol(Drug information on haloperidol) and risperidone(Drug information on risperidone)) as a specific antihostility agent.³⁸ Not surprisingly, clozapine is recommended by the American Psychiatric Association's practice guidelines for both persistent suicidal ideation or behavior and persistent hostility and aggressive behavior.³⁶

Medications such as olanzapine(Drug information on olanzapine) and quetiapine could also be considered when treating agitation or hostility; the former may be particularly helpful in the emergency department, where intramuscular olanzapine is frequently used for these purposes.

Parkinsonism and akathisia
There is no strong evidence linking extrapyramidal symptoms and suicidal behaviors. An international prospective study showed that both the severity of depression and the severity of parkinsonism were among the most predictive variables for suicidal behaviors.³⁹ These conclusions deserve a note of caution, however, since akinesia (which, along with rigidity and tremor, is part of parkinsonism) may not necessarily be related to suicide. In fact, it could be that it might even be a protective factor against suicidal behavior, although not against suicidal thinking.

On the other hand, another study failed to find any association between either akathisia or parkinsonism and suicidality in a study of patients with treatment-resistant schizophrenia.⁴⁰ A previous review also concluded that akathisia could neither be excluded as a causal factor for suicidal behaviors nor could it be unequivocally linked to it.⁴¹

Evidence for the antidepressant effect of atypical antipsychotics
Since treatment of depressive symptoms gathers the highest level of evidence, the specific profile of each atypical antipsychotic has been reviewed and summarized in Table 3. Flupentixol(Drug information on flupentixol) and amisulpride(Drug information on amisulpride) are included in this section since some interesting data have appeared on these drugs and some authors consider them as partial atypicals.

Many clinicians would agree that olanzapine should be considered when treating depressive symptoms in patients with schizophrenia or with an affective psychosis. The evidence for this assertion comes from 2 empowered, randomized, double-blind studies. In the first study, improvements were found in depressive symptoms with both haloperidol and olanzapine; patients treated with the latter showed significantly greater reductions in depressive symptoms.⁴² A second, more recent study in patients with schizophrenia or schizoaffective disorder found that patients treated with olanzapine and ziprasidone showed significant improvement in prominent depressive symptoms. Although group differences were not statistically significant, a significantly higher proportion of patients who received olanzapine completed the study and continued taking the medication longer, compared with patients who received ziprasidone.⁴³