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Letter to the Editor

Depression as a Factor in Nonadherence in Schizophrenia

Hirofumi Hirakawa, MD,a and Nobuyoshi Ishii, MDa

Published: June 16, 2020

See reply by Kane and Correll and article by Kane and Correll

To the Editor: We read with interest the article by Kane and Correll1 on optimizing treatment choice in schizophrenia to improve adherence, which suggested that long-acting formulations of antipsychotics can be a very powerful strategy in helping to ensure that patients benefit from the medication they have been prescribed. The authors discussed nonadherence, which may be related to patient factors, treatment characteristics, or the overall medical condition of the patient. To provide further insight into this issue, herein we discuss comorbid depression as a potential cause for nonadherence in schizophrenia.

Psychiatric comorbidities are common among individuals with schizophrenia, and it is estimated that comorbid depression occurs in 50% of these patients.2 Additionally, a recent study3 revealed that patients with nonaffective psychosis have high levels of worry (67.7%) and low levels of self-esteem (62.1%). Further, patients’ preferred treatment targets were feeling happier (63.2%), worrying less (63.1%), and increasing their self-confidence (62.1%).3 On the basis of these results, depression and subthreshold depression in schizophrenia might have an even higher prevalence than has been estimated. Indeed, a systematic review4 assessed the reasons for nonadherence to antipsychotics, categorizing them into intentional or unintentional. Depression is one of the main reasons for unintentional nonadherence, which exacerbates symptoms of schizophrenia.4 Since depression may impact cognitive functions, energy, and motivation, it may also affect patients’ willingness and ability to adhere to their treatment.5 Thus, clinicians should pay attention to comorbid depression as a factor in nonadherence in schizophrenia.

Furthermore, second-generation antipsychotics (SGAs) may have a direct effect on depressive symptoms in patients with schizophrenia.2 Recent network meta-analysis of placebo-controlled and head-to-head randomized controlled trials in adults with acute symptoms of schizophrenia revealed that SGAs significantly reduced depressive symptoms compared with placebo.6 Long-acting injectable (LAI) preparations of the SGAs have all demonstrated superiority over placebo and are comparable to their oral counterparts in terms of safety and tolerability.7 Therefore, we recommend using LAI SGAs for patients with schizophrenia and comorbid depression.

aDepartment of Neuropsychiatry, Oita University Faculty of Medicine, Yufu-city, Oita, Japan

Published online: June 16, 2020.

Potential conflicts of interest: The authors declare no conflicts of interest.

Funding/support: None.

J Clin Psychiatry 2020;81(4):20lr13262

To cite: Hirakawa H, Ishii N. Depression as a factor in nonadherence in schizophrenia. J Clin Psychiatry. 2020;81(4):20lr13262.

To share: Clin Psychiatry 2020;81(4):20lr13262

© Copyright 2020 Physicians Postgraduate Press, Inc.


1.Kane JM, Correll CU. Optimizing treatment choices to improve adherence and outcomes in schizophrenia. J Clin Psychiatry. 2019;80(5):IN18031AH1C. PubMed CrossRef

2.Buckley PF, Miller BJ, Lehrer DS, et al. Psychiatric comorbidities and schizophrenia. Schizophr Bull. 2009;35(2):383-402. PubMed CrossRef

3.Freeman D, Taylor KM, Molodynski A, et al. Treatable clinical intervention targets for patients with schizophrenia. Schizophr Res. 2019;211:44-50. PubMed CrossRef

4.Velligan DI, Sajatovic M, Hatch A, et al. Why do psychiatric patients stop antipsychotic medication? a systematic review of reasons for nonadherence to medication in patients with serious mental illness. Patient Prefer Adherence. 2017;11:449-468. PubMed CrossRef

5.DiMatteo MR, Lepper HS, Croghan TW. Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence. Arch Intern Med. 2000;160(14):2101-2107. PubMed CrossRef

6.Huhn M, Nikolakopoulou A, Schneider-Thoma J, et al. Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi-episode schizophrenia: a systematic review and network meta-analysis. Lancet. 2019;394(10202):939-951. PubMed CrossRef

7.Jann MW, Penzak SR. Long-acting injectable second-generation antipsychotics: an update and comparison between agents. CNS Drugs. 2018;32(3):241-257. PubMed CrossRef

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