Table 3
Normal sleep architecture, which can be disordered in schizophrenia
| Nonrapid eye movement (NREM) sleep | |
| Stage 1 | Drowsiness; represents transition between waking and sleeping |
| Stage 2 | Sleep deepens |
| Stages 3 and 4 | Deepest levels of NREM sleep subjects are most difficult to arouse (slow-wave or delta sleep) |
| Rapid eye movement (REM) sleep | |
| Vivid dreams; pulse and respiration rates are higher and more variable than during NREM sleep | |
| During the second half of the night, slow-wave sleep decreases compared with the first half of the night, but REM periods become more frequent and prolonged. | |
Managing excessive sedation
Take steps to minimize bothersome sedation in patients taking antipsychotics (Figure). To reduce daytime sedation, instruct the patient to take all or most of the antipsychotic dose at bedtime. Also rule out medical conditions that can produce fatigue and sedation, such as hypothyroidism, obstructive sleep apnea (OSA), and restless legs syndrome.
Figure
Managing sedation in patients with schizophrenia
Review the patient’s medication list to determine if other potentially sedating medications can be reduced or eliminated. Psychotropics that can cause sedation include:
- antidepressants such as the tricyclics and mirtazapine
- mood stabilizers (particularly valproic acid, but also carbamazepine, lithium, and lamotrigine).
Also consider gradually reducing the patient’s antipsychotic dose, and closely monitor for worsening of psychosis.
If sedation persists despite these interventions, consider switching the patient to a less sedating antipsychotic such as ziprasidone or aripiprazole. If these efforts also are ineffective, caffeine or off-label bupropion—75 to 100 mg once in the morning or up to twice daily—might help the patient feel more alert. Many patients taking antipsychotics drink several cups of coffee every morning to feel less sedated.
Stimulants. A consensus guideline on treating schizophrenia20 recommends prescribing amphetamine-related stimulants for patients who are persistently sedated, but this practice is highly controversial. Many stimulants increase dopamine release in the CNS, which theoretically can worsen psychosis. A clinician could be held liable for the actions of patients medicated with stimulants.
Modafinil is a nonamphetamine CNS stimulant approved for use in disorders of excessive sleep such as narcolepsy, OSA, shift work sleep disorder, and fatigue related to multiple sclerosis. Its mechanism of action in promoting wakefulness in these disorders is not fully understood; it may activate histaminergic projections in the frontal cortex from the tuberomammillary nucleus, which plays a major role in maintaining wakefulness.21
Modafinil, 200 mg in the morning, has been reported to reduce total sleep time without adverse effects in 3 patients experiencing sedation associated with antipsychotics.22 A later double-blind, placebo-controlled trial by Sevy et al23 found that modafinil and placebo were associated with similar, significant improvement in fatigue over time. Narendran24 reported a case in which modafinil might have exacerbated psychosis in a patient with schizophrenia who was taking 200 mg qid.
Managing chronic insomnia
Schizophrenia patients with chronic insomnia usually require education about appropriate sleep habits, combined with additional treatments.
Sleep hygiene. Instruct patients to:
- Wake up at the same time every day, regardless of when they went to sleep.
- Maintain a consistent bedtime.
- Exercise regularly, preferably in the late afternoon but not within 2 to 4 hours of bedtime.
- Perform relaxing activities before bed.
- Keep the bedroom quiet and cool (extreme temperatures compromise sleep).
- Do not watch the clock at night.
- Avoid caffeine and nicotine for at least 6 hours before bedtime.
- Drink alcohol only in moderation, and avoid use for at least 4 hours before bedtime.
- Avoid napping; it may interfere with the ability to fall asleep at night.
Medications. The consensus guideline on treating schizophrenia20 offers the option of switching the patient with chronic insomnia to one of the more sedating antipsychotics, such as olanzapine, quetiapine, or clozapine. Sedation alone should not be the reason to switch to clozapine, however.
You could consider adding a bedtime sedative to the patient’s medications (Table 4). FDA-approved sedatives include nonbenzodiazepines such as zolpidem, zolpidem extended-release, zaleplon, or eszopiclone, and the melatonin receptor agonist ramelteon. Although not approved as sedatives, some antidepressants such as trazodone or mirtazapine and antihistamines such as diphenhydramine and hydroxyzine are used to promote sleep. Benzodiazepines can be helpful but require caution when prescribed to patients with comorbid substance abuse disorders.
Sedatives have been studied extensively in general populations with insomnia but not in patients receiving antipsychotics. Combining antipsychotics and sedatives can produce daytime drowsiness and sedation.