This week, Mad in America examines four studies around the harmful effects linked to antipsychotics. The first finds that off-label, long-term antipsychotic use is linked to weight gain, abnormal blood sugar and lipid levels, and death related to heart and metabolic issues. The second finds that nearly one-third of antipsychotic users report movement disorders. The third links negative side effects of antipsychotics to reduced ability to navigate daily life and lower happiness. The fourth finds that two-thirds of drug-naive participants reported sexual dysfunction after starting antipsychotics.
Off-Label, Long-Term Antipsychotic Use Linked to Weight Gain, Abnormal Blood Sugar, and Heart Risks
A new article published in Psychiatry Research finds that off-label, low-dose, long-term antipsychotic use is associated with weight gain, abnormal blood glucose and lipid levels, and death related to heart disease, high blood pressure, and metabolic disorders like type 2 diabetes. This study, led by Ramya Padmavathy Radha Krishnan from the University of Sydney in Australia, also reports a link to increased risk of high blood pressure and metabolic syndrome.
Off-label use is when a drug is used for an indication that has not been approved by the FDA. It is a common practice in US healthcare. For antipsychotics specifically, the researchers write, “Off-label antipsychotic prescribing is often used to manage specific symptoms such as agitation, insomnia, anxiety or irritability, rather than addressing the underlying disorder.”
The authors conducted a systematic review of 13 observational studies that examined antipsychotic use for more than a year in adults that did not have a psychotic disorder diagnosis. The authors found no randomized controlled trials that fit the inclusion criteria.
Higher prevalence of weight gain, high blood sugar, and abnormal blood lipid levels were observed in people taking off-label, low-dose, long-term antipsychotics. Weight gain prevalence ranged between 28.8% – 77.9% in antipsychotic users compared to 17.8% – 71.9% in non-users. High blood sugar was observed in 4.8% – 23.2% of users compared to 0 – 9.7% of non-users. Abnormal blood lipids were present for 15.8% – 47.5% of users compared to 11.2% – 29.3% of non-users. Low dose use was also linked to a 21% increased risk of death related to heart and metabolic problems in one included study. Additionally, one study linked long-term, off-label use to high blood pressure (38.4% of users compared to 24.3% on non-users) and metabolic syndrome (28.2% compared to 14.4%).
This research had five main limitations. Included studies used varying methods, preventing the authors from conducting a meta-analysis. The evidence collected by the authors came from observational studies, meaning these findings cannot definitively say that antipsychotic use causes the observed negative effects. Some included studies did not include participants’ treatment histories or baseline cardiometabolic risks. Included studies had relatively short follow-up periods for some subgroups. The authors only included studies published in English.
Nearly One-Third of Antipsychotic Users Report Movement Disorders
A new study published in Comprehensive Psychiatry finds that nearly one-third of people diagnosed with “severe mental illness” and treated with antipsychotics in Africa report antipsychotic-induced movement disorders. This research, led by Zemene Yiglet from the University of Gondar in Ethiopia, identified drug-induced Parkinsonism as the most commonly reported movement disorder.
The authors conducted a systematic review and meta-analysis of 22 observational studies from African nations involving movement disorders in people with diagnoses such as schizophrenia and bipolar disorder.
Overall, 32.2% of participants treated with antipsychotics reported antipsychotic induced movement disorders. Drug-induced Parkinsonism (22.7%) was the most commonly reported disorder, followed by akathisia (11.9%), tardive dyskinesia (10.7%), and acute dystonia (9.5%). The authors also identified four significant predictors of developing antipsychotic induced movement disorders, including female sex (3.6 times higher odds), high antipsychotic dose (3.2), longer duration of antipsychotic use (3.2), and using substance like alcohol, cannabis, and stimulants (2.8)
This research had four main limitations. The included studies used various designs, clinical settings, participant populations, and measures. The majority of included studies were cross-sectional, making it difficult to identify acute onset reactions. The results cannot definitively say that antipsychotics are causing movement disorders. This research looked specifically at six African nations (Ethiopia, South Africa, Nigeria, Tunisia, Uganda, and Kenya), limiting generalizability to other populations.
Antipsychotics Linked to Reduced Ability to Navigate Daily Life and Lower Happiness
A new study from the Netherlands published in Schizophrenia Bulletin finds that antipsychotic adverse effects, total dose, and taking more than one antipsychotic drug simultaneously are linked to reduced ability to participate in everyday life. This research, led by Stijn Crutzen from the University of Groningen in the Netherlands, also reports that adverse effects from antipsychotics are associated with lower happiness.
The authors used data from the Pharmacotherapy Monitoring and Outcome Survey to conduct a longitudinal study of 2,490 people receiving long-term care at one of four mental health facilities in the northern Netherlands. This data covered the years from 2013 to 2021, but not every participant was followed for the duration of the study.
Having more negative effects from antipsychotics, higher total dose, and using more than one antipsychotic simultaneously were all linked to poorer ability to navigate daily life. Negative effects on cognition, mood, and anticholinergic negative effects such as dry mouth, constipation, and blurred vision were most linked to reduced ability to participate in everyday life.
Having more negative effects from antipsychotics was also linked to reduced happiness. Sexual dysfunction, impaired cognition, worse mood, sedation, and physical effects such as muscle stiffness were most strongly linked to reduced happiness. Higher antipsychotic dose was associated with reduced happiness before adjusting for age, sex, duration of symptoms, and positive psychotic symptoms, but the link did not remain after adjustment.
This study had three main limitations. The observational design means the results cannot say for sure that antipsychotics caused reduced ability to navigate daily life or lower happiness. Other unmeasured variables could have affected the results. Negative effects were self-reported, which exposes the data to possible bias due to misremembering and misreporting. The participants all came from four psychiatric facilities in the northern Netherlands, limiting generalizability to other populations.
Sexual Dysfunction Reported by Two-Thirds of Drug-Naive Participants After Starting Antipsychotics
A new Indian study published in the Journal of Clinical and Diagnostic Research finds two-thirds of drug-naive participants reported sexual dysfunction as a negative effect of antipsychotic use. Weight gain, sedation, and drug induced movement disorders were also commonly reported. This research, led by Nisheet Patel from Sumandeep Vidyapeeth University in India also finds increases in overall negative effect burden, body weight, body mass index, and total cholesterol over three months of antipsychotic use.
The authors recruited 332 patients aged 18 – 70 years from the psychiatry department at Dhiraj Hospital in Gujarat, India. Participants were required to have a diagnosed psychotic disorder for which they received an antipsychotic prescription and no previous exposure to antipsychotic drugs. They underwent metabolic measurement (weight, BMI, blood glucose, cholesterol, etc.) and were assessed for negative effects including sexual dysfunction and movement disorders before starting antipsychotics, and again at one and three months after initiating antipsychotic treatment.
Sexual dysfunction was the most common negative effect reported by participants, with an overall prevalence rate of 66% at three months. Weight gain (60% of participants), sedation (50%), and movement-related symptoms such as rigidity, tremor, and abnormal gait (45%) were also common. Over the three-month follow-up, participants gained an average of 5.68 kg (12.79 lbs), saw their BMI increase from 24.0 to 25.8, and saw their total cholesterol increase from 150.2 to 173.5. The authors also reported that 9.9% of participants had involuntary movements detected by the Abnormal Involuntary Movement Scale, a clinician reported assessment used to detect tardive dyskinesia.
This research had three main limitations. All participants came from a single psychiatric department in India, limiting generalizability. The three-month follow-up period was too short to evaluate long-term adverse effects. While the follow-ups provide some evidence that the reported negative effects were caused by antipsychotic use, the observational nature of the study means there could have been other unmeasured factors that affected the results. These results cannot establish definitively that the observed negative effects were caused by antipsychotics.
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Crutzen, S., Gangadin, S., Hua, K. H., Visser, E., Jörg, F., Pijnenborg, G. H., van der Meer, L., Veling, W., & Castelein, S. (2025). The Association of antipsychotic treatment and side effects with societal recovery and Happiness: A naturalistic cohort study of people in long-term care for a psychotic disorder. Schizophrenia Bulletin, 52(4). (Link)
Patel, N., Kataria, L., Jain, A., Sarvaiya, D., Kalathiya, P., & Palker, D. (2026). Antipsychotic-induced side-effects among Indian patients: A prospective observational study. Journal of Clinical and Diagnostic Research. (Link)
Radha Krishnan, R. P., Dzidowska, M., Zheng, D., Russell, D. J., Rhaman, A., Quintrell, E., Chan, C. H., Buckley, N. A., & Raubenheimer, J. E. (2026). Long-term antipsychotic use and cardiometabolic adverse effects in adults with non-psychotic disorders: A systematic review. Psychiatry Research, 364, 117299. (Link)
Yiglet, Z., Kibralew, G., Tadesse, H., Molla, W., Workie, Y., Demelash, D., Fasil, B., Sahle, A., Demelash, D., Endeshaw, W., Getnet, M., & Kelebie, M. (2026). Antipsychotic-induced movement disorders among patients with severe mental illness in Africa: A systematic review and meta-analysis. Comprehensive Psychiatry, 151, 152744. (Link)
