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Treatment trials for negative symptoms in schizophrenia
Louise Birkedal Glenthøj1,2, Mette Ødegaard Nielsen3,4, Merete Nordentoft4,5
1VIRTU Research Group, Mental Health Centre Copenhagen, Copenhagen University Hospital - Mental Health Services CPH.
Current Opinion in Psychiatry
|January 16, 2026
Summary
Negative symptoms in schizophrenia are treatable, with modest improvements seen in recent trials using exercise, psychosocial, and digital interventions. Further research is needed for optimal treatment strategies.
Area of Science:
- Psychiatry and Neuroscience
- Clinical Psychology
- Rehabilitation Medicine
Background:
- Negative symptoms of schizophrenia represent a significant unmet clinical need.
- Existing pharmacological and psychosocial interventions offer modest efficacy for negative symptoms.
- A comprehensive review of recent randomized clinical trials (RCTs) is warranted.
Purpose of the Study:
- To review RCTs published between January 2024 and October 2025 targeting negative symptoms in schizophrenia.
- To evaluate pharmacological, psychosocial, physical, digital, and neuromodulatory interventions.
- To synthesize current evidence on the efficacy and feasibility of novel treatments.
Main Methods:
- Systematic review of randomized clinical trials (RCTs).
- Inclusion of studies published between January 2024 and October 2025.
- Categorization of interventions into pharmacological, psychosocial, physical, digital, and neuromodulatory approaches.
Main Results:
- Most RCTs were small and heterogeneous, showing modest effects on negative symptoms.
- Exercise, psychosocial, and digital interventions demonstrated feasibility and within-group improvements, but rarely outperformed controls.
- Pharmacological trials showed mixed results; neuromodulation (e.g., intermittent theta burst stimulation) indicated small to moderate benefits.
- Cognitive remediation did not directly reduce negative symptoms but influenced functional outcomes.
Conclusions:
- Negative symptoms in schizophrenia are modifiable.
- There is a need for larger, mechanism-informed, multimodal trials with long-term follow-up.
- Current evidence supports a range of interventions, highlighting the potential for combined treatment approaches.
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