Antipsychotic Side Effects Tough to Take, Patients Say

Megan Brooks

May 28, 2019

SAN FRANCISCO — Side effects from second-generation antipsychotic (SGA) medications have a considerable negative impact on daily functioning and quality of life in patients with schizophrenia, according to a large survey of patients.

"The survey confirms that stable patients taking SGAs are living with many disruptive side effects," Catherine Weiss, PhD, Otsuka Pharmaceutical, Princeton, New Jersey, told Medscape Medical News. These include activating (tremor, restlessness, difficulty sleeping) and sedating (feeling sleepy, "drugged", and dizzy) side effects, sexual side effects, and weight gain.

"This survey also highlights the importance of capturing the patient's perspective when evaluating the impacts of second-generation antipsychotics," said Weiss.

She presented the results May 21 at the American Psychiatric Association (APA) 2019 Annual Meeting.

Granular Data

SGAs generally have fewer motor side effects than first-generation antipsychotics, but are associated with other well-known side effects, including akathisia, sedation, metabolic abnormalities, weight gain, and sexual dysfunction. Many of these side effects lead to poor adherence or discontinuation, but less is known about their impact on daily functioning and emotional wellbeing.

"We don't really know, at the granular level, how patients function on SGAs. With this survey, we really tried to understand specifically what domain or domains of functioning are affected. What jumps out is that basically every domain is affected. Physical functioning, social functioning, and emotional functioning," said Weiss.

A total of 435 patients with schizophrenia from the United States, Canada, Australia, and Europe completed the online survey. They had been taking an SGA for 7.8 months on average and were stable on the medication.

Side effects according to the Glasgow Antipsychotic Side Effect Scale (GASS) were common, with difficulty sleeping and being sleepy during the day the most common.

Side Effects Associated With SGAs

Side effect Everyday, % A few times, % Once, %
Sleepy during the day 24.9 47.5 11.1
Difficulty sleeping 15.9 45.5 13.3
Mouth dry 15.9 32.6 15.7
Feeling drugged/zombie-like 9.9 28.0 16.6
Heart beating irregularly/fast 5.3 37.0 11.8
Dizzy on standing/fainting 5.1 29.3 19.6
Problems enjoying sex 11.8 28.2 13.4
Tense or jerky muscles 10.2 29.9 12.5
Very thirsty/urinate often 12.9 27.3 12.0
Vision blurry 6.4 29.7 15.2
Legs restless/can't sit still 11.3 27.8 12.0
Hands or arms shaky 5.8 29.0 13.9


Over half (52.4%) of patients reported gaining weight. These and other side effects all contribute to a significant burden on daily functioning (physical, social, vocational, and emotional) and quality of life satisfaction, including on work, sexual drive, and psychosocial effects, Weiss said.

Activating and sedating side effects, as well as weight gain and problems enjoying sex, were weakly to moderately correlated with poorer quality of life and satisfaction. 

Frustrating, Embarrassing

"Frustrated" was the most common emotion used to describe SGA side effects. Weiss said some of the individual comments from the patients who took the survey really highlight the negative impact of side effects on everyday life.

For example, a patient with shaky hands said, "It embarrasses me, so I don't like meeting people or going to appointments." A patient who feels drugged/zombie-like said, "It's difficult to perform everyday things like washing, cooking, etc." A patient who experiences restlessness on the medication said, "It creates (gives) me anxiety and I cannot understand why, it scares me and prevents me from continuing to do any work."

These personal comments are "important because doctors often don't really know or understand how their patient feels about the side effects," Weiss told Medscape Medical News.

"This was a fairly well-functioning cohort; most are employed, they don't live with their parents, they live often with a spouse or have a family, yet they really aren't doing that well on antipsychotics. We need better antipsychotics," said Weiss.

René S. Kahn, MD, PhD, chair of the department of psychiatry, Icahn School of Medicine at Mount Sinai, New York City, agrees. 

"Outside of drugs, there is not much we can do for schizophrenia. Drugs by far are the biggest mainstay of treatment and we need new and better drugs for schizophrenia," he told Medscape Medical News.

On that front, the US Food and Drug Administration recently granted breakthrough therapy designation to a potentially first-in-class psychotropic agent with a completely different mechanism of action of currently available antipsychotic agents that may have far fewer side effects.

The drug, known as SEP-363856, is being developed by Sunovion Pharmaceuticals and PsychoGenics. SEP-363856 does not work through direct dopamine-2 antagonism and the phase 2 study showed that it is efficacious and has an adverse event profile similar to placebo, as reported by Medscape Medical News.

"Because this drug is unrelated to dopamine, it doesn't have the same side effects. It may not have any, we'll have to wait and see," said Kahn.

The study was funded by Otsuka Pharmaceutical Development & Commercialization and Lundbeck. Weiss is an employee of Otsuka Pharmaceutical. Kahn has reported financial relationships with Alkermes, Merck, Minerva Neuroscience, Lundbeck, Otsuka, Teva, and Janssen.

APA 2019. Presented May 21, 2019. Abstract 64.

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