Methamphetamine Use and Antipsychotic-related Extrapyramidal Side-effects in Patients with Psychotic Disorders

Abstract

Objective: Extrapyramidal side-effects (EPSE) are frequent in patients treated with antipsychotics and comorbid substance use disorders (SUDs). Methamphetamine has been shown to act as a dopaminergic neurotoxin. We aimed to determine whether EPSE occur more often in patients with psychotic disorders and co-occurring methamphetamine (MA) use disorders, and we examined the relationship between MA use, antipsychotic type, dose and EPSE. Methods: This study was a secondary analysis of data from three separate primary studies. Across all studies, psychiatric and SUD diagnoses were determined using the SCID-I for DSM-IV. EPSE were determined using the Simpson-Angus Scale (SAS) for Parkinsonism, the Barnes Akathisia Rating scale (BARS), and the Abnormal Involuntary Movement Scale (AIMS) for tardive dyskinesia. Participants were classified as having any EPSE if they scored above the cutoff on any of the EPSE scales (SAS, BARS, AIMS). We analyzed data using multivariable logistic regression analysis. Results: The sample included 102 patients with non-affective or affective psychotic disorders. Of the total sample, 65.7% were male, 54.9% had schizophrenia spectrum disorders, 20.5% bipolar type I disorder with psychotic features, 11.7% schizoaffective disorder and 12.7% had substance-induced psychosis. A diagnosis of a methamphetamine use disorder (abuse or dependence) was present in 25.5% of participants. EPSE occurred in 38.2% of patients and were significantly associated with MA use in the unadjusted and adjusted analysis, OR_adj = 4.01, 95% CI [1.07, 14.98], p = .039. Patients with MA dependence and MA use >3 years were significantly more likely to have EPSE. We found a significant interaction effect between MA use disorders and standardized antipsychotic dose on the occurrence of EPSE, OR_adj = 1.01, 95% CI [1.00, 1.01], p = .042, with MA users having a disproportionally higher likelihood of having EPSE compared to MA non-users as antipsychotic dosage increased. There were no significant associations of EPSE with comorbid alcohol, cannabis, or methaqualone use disorders. Conclusions: Patients with a MA use disorder were significantly more likely to have EPSE with evidence for a dose-response effect. Clinicians should carefully titrate antipsychotic dosage from lower to higher doses to avoid EPSE in patients with MA use disorders.

KEYWORDS:

• Psychosis
• methamphetamine
• extrapyramidal side-effects
• substance use

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Acknowledgments

We would like to thank Dr. Nyameka Dyakalashe, Lungiswa Mankayi, Ziyaan Noordien and Beau Broekhof for their assistance.

Disclosure statement

Henk Temmingh, Fleur Howells and Goodman Sibeko have not received any financial or commercial related compensation that can be considered to represent a conflict of interest. Dan J. Stein (DJS) is supported by the Medical Research Council of South Africa and has received research grants and/or consultancy honoraria from: Abbott, Astrazeneca, Eli-Lilly, GlaxoSmithKline, Jazz Pharmaceuticals, Johnson & Johnson, Lundbeck, Orion, Pfizer, Pharmacia, Roche, Servier, Solvay, Sumitomo, Sun, Takeda, Tikvah, and Wyeth. DJS is also on the scientific advisory board of the TLC Foundation for Body-Focused Repetitive Behaviors, the Anxiety and Depression Association of America (ADAA), and the South African Depression and Anxiety Support Group. Wim van den Brink reports personal fees from Lundbeck, Eli Lilly, Pfizer, Takeda, Novartis, Mundipharma, Indivior, Angelini, D&A Pharmaceuticals, and Opiant Pharmaceuticals.

Additional information

Funding

The Presentation and Risk Factors in the Psychobiology of Psychosis (PRP) study received funding from the University of Cape Town, Department of Psychiatry and Mental Health Research Committee. The Cortical Inhibition and Attentional Modulation (CIAM) study received funding from the National Research Foundation of South Africa and the University of Cape Town, Department of Psychiatry and Mental Health Research Committee. The Social Inclusion in Psychosis study (SIP) received funding from the World Psychiatric Association and the University of Cape Town, Department of Psychiatry and Mental Health Research Committee.