A review on side effect management of second-generation antipsychotics to treat schizophrenia: a drug safety perspective

ABSTRACT

Introduction

Effective side effects management present a challenge in antipsychotic treatment with second-generation antipsychotics (SGAs). In recent years, most of the commonly used SGAs, except for clozapine, have been shown to differ only slightly in their effectiveness, but considerably regarding perceived side effects, safety profiles, and compatibility to preexisting medical conditions.

Areas covered

The current state of available evidence on side-effect management in SGA treatment of patients with schizophrenia spectrum disorders (SSD) is reviewed. In addition, current guideline recommendations are summarized, highlighting evidence gaps.

Expert Opinion

SGA safety and side effects needs to be considered in treatment planning. Shared decision-making assistants (SDMA) can support patients, practitioners and relatives to orient their decisions toward avoiding side effects relevant to patients’ adherence. Alongside general measures like psychosocial and psychotherapeutic care, switching to better tolerated SGAs can be considered a relatively safe strategy. By contrast, novel meta-analytical evidence emphasizes that dose reduction of SGAs can statistically increase the risk of relapse and other unfavorable outcomes. Further, depending on the type and severity of SGA-related side effects, specific treatments can be used to alleviate induced side effects (e.g. add-on metformin to reduce weight-gain). Finally, discontinuation should be reserved for acute emergencies.

KEYWORDS:

• Safety aspects
• schizophrenia
• second-generation antipsychotics (SGA)
• side effect management
• shared decision making assistants (SDMA)

Article highlights

• Antipsychotic treatment agents classified as second-generation antipsychotics (SGAs) are distinguished more by their side effect profile rather than their efficacy in managing psychotic symptoms.

• Effective side effect management presents a key challenge to facilitate patient’s adherence to SGA treatment.

• Shared decision-making assistants (SDMA) can support practitioners, patients and their relatives to steer their decision-making process toward avoiding side effects most relevant for patients’ adherence.

• Switching to better tolerated SGAs or adding specific treatments for side effect management are considered safe strategies. By contrast, novel evidence emphasizes that dose reduction of SGAs statistically increases the risk of relapse and other unfavorable outcomes.

• Abrupt discontinuation of SGA treatment should be reserved for acute emergencies.

Declaration of interest

W Strube has received a paid speakership from Mag & More (Neurocare), Recordati and Rovi. He was a member of an advisory board of Recordati. E Wagner was a member of advisory boards of Recordati and Boehringer Ingelheim. A Hasan was a member of advisory boards of Boehringer Ingelheim, Lundbeck, Janssen, Otsuka, Rovi and Recordati and received paid speakership by these companies as well as by AbbVie and Advanz. He is the editor of the German schizophrenia guideline.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Author contribution

W. Strube took the lead in writing the manuscript with support from E. Wagner and J. Luykx. A. Hasan supervised the project. All authors provided critical feedback and helped shape the research, analysis of eligible data and the composition of the manuscript.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The project was carried out using the clinical trials infrastructure of the DZPG [German Center for Mental Health] [FKZ: 01EE2303C].