Among SGAs, a double-blind, placebo-controlled, crossover study of the effects of ziprasidone, 40 mg/d, on sleep in a group of healthy volunteers found a significant increase in total sleep time and sleep efficiency.9 A double-blind trial compared patients taking low, medium, or high daily doses of olanzapine with patients receiving haloperidol or placebo.10 Sedation was reported in 20% of patients taking low doses of olanzapine (5 ± 2.5 mg/d) compared with 29.7% on medium doses (10 ± 2.5 mg/d) and 39.1% on high doses (15 ± 2.5 mg/d).10
A double-blind, placebo-controlled, crossover study demonstrated that olanzapine produced significant increases in sleep continuity, slow wave sleep, and subjective ratings of sleep quality in healthy men.11 Similarly, a study comparing haloperidol, 12 mg/d, and quetiapine, 75 to 750 mg/d, for treating acute schizophrenia found an 8% to 11% incidence of somnolence in the quetiapine group compared with 6% and 8% in the haloperidol and placebo groups, respectively.12 Somnolence was reported as an adverse event in these studies, which were designed to examine the drug’s effect on acute schizophrenia and did not evaluate its effect on sleep.
A double-blind, placebo-controlled, crossover study examining quetiapine’s effects on sleep in 14 healthy patients demonstrated a significant difference in total sleep time, sleep period time, and sleep efficiency.13 Similarly, an open-label pilot study of quetiapine’s effect on primary insomnia showed significant improvement in total sleep time and sleep efficiency.14
Studies examining quetiapine’s effects on insomnia in patients with substance abuse15 and women with localized breast cancer16 showed improved sleep scores on multiple assessment tools, while an open-label study of quetiapine for Parkinson’s disease demonstrated decreased sleep latency.17 Adjunctive quetiapine administered over a 6-week, open-label trial in veterans with posttraumatic stress disorder revealed significant improvement from baseline in sleep quality and duration and diminished dreaming.18
Sedating antipsychotics such as thioridazine and chlorpromazine historically were used off-label for insomnia, but fell out of favor because of their associated cardiac risks. More recently, clinicians have been using SGAs in a similar manner19 even though SGAs are costly and have significant risks such as metabolic problems.
Studies supporting the use of SGAs for the short-term or long-term treatment of insomnia are limited by small sample sizes or open-label designs.20 In 2005 the National Institutes of Health State-of-the-Science Conference Panel did not recommend using SGAs for treating chronic insomnia.21
Tics in Tourette’s disorder
FGAs and SGAs have been used to treat tics associated with Tourette’s disorder (TD).22 Haloperidol is FDA-approved for treating tics in adult and pediatric patients with TD. Many studies have reported the efficacy of haloperidol in this population; however, cognitive blunting, weight gain, lethargy, and akathisia limit its use.23
Pimozide, the most widely used alternative to haloperidol for treating TD, can cause clinically significant QTc prolongation and sudden death. Penfluridol demonstrated significant symptomatic improvement compared with haloperidol in 1 study, but its carcinogenic potential limits its use.24
A double-blind, placebo-controlled study comparing fluphenazine and trifluoperazine with haloperidol for treating TD showed that both are significantly more effective than placebo, but none was more effective than the others.25 Studies show chlorpromazine, perphenazine, and thioridazine are less effective than haloperidol and their use is limited by photosensitivity, dermatitis, EPS, and blood and liver dyscrasias.26
Risperidone is superior to placebo for treating tics associated with TD.27 A placebo-controlled trial of ziprasidone showed the drug has efficacy similar to risperidone in reducing tics in children and adolescents with TD.28 However, ziprasidone is not FDA-approved for this use.
Evidence supporting the use of other SGAs for treating TD is more limited. Several small studies of olanzapine and aripiprazole had limited but favorable results. Quetiapine has not been studied for treating TD, but several case reports have indicated a positive response. In a double-blind, placebo-controlled trial, clozapine showed no therapeutic benefit for TD.29
Delirium
American Psychiatric Association practice guidelines suggest using psychotropic medications to treat neuropsychiatric symptoms of delirium.30 Antipsychotics are considered first-line agents that lower hospital mortality rates, decrease lengths of hospital stays, and improve delirium symptoms, in some cases before the underlying medical etiologies resolve.30,31 Available in liquid, oral, IM, and IV formulations, haloperidol is the mainstay of symptomatic treatment of delirium.31 Although not FDA-approved, it is recommended by the Society of Critical Care Medicine as a safe, cost-effective, and efficacious therapy for the psychiatric symptoms associated with delirium.