Clozapine Sleepiness, Bedwetting, and a Fast Heart Rate: Rates and Treatment Evidence

Creator: Ryan S. Sultan, MD
Published: 2026-11-12

By Ryan S. Sultan, MD
Psychiatrist · Columbia University Irving Medical Center
Published November 12, 2026 · 6-minute read

Drowsiness or sedation was reported by 39% of 842 patients across Clozaril clinical studies. Tachycardia was reported by 25%, a rate the label bases on approximately 1,700 patients exposed before marketing.¹ In a cohort study where doctors asked directly, 17 of 82 patients taking clozapine (20.7%) reported bedwetting.²

A placebo-controlled trial of modafinil for wakefulness was negative, a bedwetting treatment review found case reports and case series, and a Cochrane review of treatments for clozapine tachycardia found no trial to include.^{3, 4, 5} Whether to adjust the dose or add a medication is the prescriber's decision.

How common sleepiness is on clozapine

Sedation and tachycardia rates in the Clozaril label
Trials	Sedation	Tachycardia
6-week trial: clozapine (N=126) and chlorpromazine (N=142)	21% and 13%	17% and 11%
All Clozaril studies except InterSePT (N=842)	39% (drowsiness or sedation)	25%, based on approximately 1,700 patients exposed before marketing
2-year InterSePT trial: clozapine (N=479) and olanzapine (N=477)	46% and 25% (somnolence)	Not listed

Source: Clozaril prescribing information, Tables 9 to 11, revised June 2025.¹

A 2025 meta-analysis of 22 randomized trials with 2,991 patients found somnolence in 36.3% of those on clozapine and 21.9% of those on other antipsychotics (odds ratio 2.06, 95% CI 1.65 to 2.57). Clozapine dose was unrelated to the association.⁶ In an observational study of 133 patients, 64.7% slept at least 9 hours daily.⁷

The label states that sedation and impaired cognitive and motor performance may be dose-related. It tells prescribers to caution patients about driving and operating hazardous machinery until they're reasonably certain clozapine doesn't affect them adversely.¹

What has been tried for clozapine sleepiness, and how often it failed

In the same observational study, a lower clozapine dose was recommended to 22 patients and added aripiprazole to 23. The majority, 81.8% and 73.9%, did not reduce the number of hours they slept. The authors concluded that both strategies "were effective only in a limited numbers of subjects".⁷

A double-blind pilot trial added modafinil up to 300 mg/d or placebo for 8 weeks in 35 stabilized outpatients taking clozapine. Modafinil didn't improve wakefulness or fatigue compared with placebo, and the authors wrote that the results "do not support routine use of modafinil".³ In a report of 3 patients given methylphenidate, all described decreased sedation over 27 to 32 months of treatment.⁸

No trial of moving the dose to bedtime was found in the literature search for this page (November 2026). In clinic datasets of 676 and 308 patients, clozapine was prescribed once daily in 75.1% and 74.4%, while the label describes divided doses.^{9, 1} Those datasets were cross-sectional and can't show whether timing changes daytime sleepiness. The schedule is set with the prescriber.

Clozapine bedwetting: about one in five in the study that asked

In a cohort study, doctors were asked to question their patients directly about bedwetting. It was reported by 17 of 82 (20.7%) taking clozapine, 11 of 115 (9.6%) taking olanzapine, 7 of 105 (6.7%) taking quetiapine, and 12 of 195 (6.2%) taking risperidone.² In a series of 57 inpatients treated with clozapine, 17 developed urinary incontinence.¹⁰

The label lists nocturnal enuresis only among postmarketing reports, with no rate. Its all-studies table has a single line for urinary abnormalities, at 2% of 842 patients.¹

In a 1994 series, five of 12 patients had nocturnal incontinence in the first 3 months of treatment, and it resolved spontaneously in all five, too few to show that it usually resolves. It was documented in the case notes for only one of them, and affected patients tended to be embarrassed and reluctant to report it.¹¹

Treatment evidence: case reports and case series

A 2023 systematic review identified 22 case reports and case series describing 74 patients and called the evidence "sparse". Its authors proposed non-drug measures first, including bathroom alarms, voiding before bedtime, and nocturnal fluid restriction, then a trial of aripiprazole, with desmopressin considered for severe refractory cases under monitoring for hyponatremia.⁴ A 2023 article in the same journal carries a title beginning "Desmopressine is and remains the drug of first choice".¹² The choice belongs to the prescriber.

A fast heart rate is common in the first month

In 123 consecutive inpatients assessed daily during clozapine titration, mean heart rate rose from 83.7 to 99.5 beats per minute. Almost all (93.5%) had at least one reading above 100, and 68% had three consecutive days above 100, the study's definition of tachycardia. At least one reading above 120 was recorded in 35.8%, and 8% had persistent rates above 120. Tachycardia resolved spontaneously for some, and 44% remained tachycardic at day 28.¹³

On long-term treatment, 33% of 174 patients on clozapine had a heart rate above 100, compared with 16% of 87 patients on long-acting injectable antipsychotics. The majority of those above 100 received no specific treatment for it.¹⁴

The label lists tachycardia among the signs that should prompt a prescriber to consider myocarditis, along with chest pain, palpitations, shortness of breath, and fever.¹ A fast heart rate in the first weeks with fever, chest pain, or breathlessness needs same-day contact with the prescriber or urgent care. The clozapine myocarditis page covers that evaluation.

Beta blockers for clozapine tachycardia: an empty Cochrane review and one small trial

A 2016 Cochrane review of drug treatments for clozapine-induced sinus tachycardia identified no study that met its inclusion criteria. It concluded, "There are currently insufficient data to confidently inform clinical practice."⁵

An open-label randomized trial published in 2026 gave 20 patients atenolol 25 mg once daily and 20 patients ivabradine 5 mg twice daily for two months. Its abstract reports that both drugs "significantly reduced pulse-rates". The trial had no placebo arm, and it was designed to compare heart rate variability.¹⁵ Whether to treat, and with what, is the prescriber's decision.

The authors of the first-month study wrote that spontaneous resolution in some patients "suggests watchful monitoring may be appropriate" before a rate-controlling drug is used.¹³ A 2013 review concluded that tachycardia, once myocarditis and neuroleptic malignant syndrome are ruled out, "can be managed and should rarely lead to clozapine discontinuation".¹⁶

Limitations of the evidence

This evidence has limitations. First, the all-studies label rates are not adjusted for duration of exposure, and the bedwetting and incontinence figures come from samples of 82, 57, and 12 patients. Second, the same November 2026 search found no placebo-controlled trial showing that a drug improves clozapine sedation, bedwetting, or tachycardia, and long-term follow-up of cardiovascular outcomes is still required.¹³ Nevertheless, all three effects are common, and each is a reason to talk with the prescriber, who decides whether the dose or anything else changes.

Frequently asked questions

How common is sleepiness on clozapine?

Across Clozaril clinical studies, drowsiness or sedation was reported by 39% of 842 patients. A 2025 meta-analysis of 22 randomized trials found somnolence in 36.3% of patients on clozapine and 21.9% on other antipsychotics.^{1, 6}

What helps with clozapine tiredness during the day?

The literature search for this page (November 2026) found no placebo-controlled trial showing that a drug helps. In an observational study, 81.8% of patients advised to lower the dose and 73.9% of those advised to add aripiprazole did not sleep fewer hours, and a modafinil trial in 35 patients found no improvement over placebo. Any change to the dose or schedule is made by the prescriber.^{7, 3}

Is bedwetting a side effect of clozapine?

It has been reported. In a cohort study where doctors asked directly, 17 of 82 patients taking clozapine (20.7%) reported bedwetting. The label lists nocturnal enuresis only among postmarketing reports, with no rate. It is something to tell the prescriber about.^{2, 1}

Is a fast heart rate normal on clozapine?

It is common. During titration, 68% of 123 inpatients had three consecutive days with a heart rate above 100, and on long-term treatment 33% of 174 patients had a heart rate above 100. A fast heart rate in the first weeks with fever, chest pain, or breathlessness needs same-day contact with the prescriber or urgent care.^{13, 14}

Do I need a beta blocker for clozapine tachycardia?

That is the prescriber's decision. A 2016 Cochrane review identified no study that met its inclusion criteria, and a 2026 trial of 20 patients on atenolol and 20 on ivabradine had no placebo arm. The authors of the first-month study wrote that watchful monitoring may be appropriate before a rate-controlling drug is used.^{5, 15, 13}

In a crisis: call or text 988, or go to the nearest emergency department. A first episode of psychosis belongs in a hospital-based or coordinated specialty care program.

I start and manage clozapine in an outpatient practice in Chelsea, Manhattan. Details are on the schizophrenia care in NYC page. Clozapine should not be stopped, skipped, or restarted without the prescriber. This page is general information and does not replace an evaluation.