In Germany, antipsychotic polypharmacy gets a green light, and psychotherapy gets a long-overdue upgrade
STUDY: Halms T et al, Der Nervenarzt 2026
STUDY TYPE: Clinical practice guideline
FUNDING: German Society for Psychiatry and Psychotherapy
Background
Germany’s S3 schizophrenia guideline have been updated for the fourth time since 2006. This version marks a shift from a static document to a “living guideline,” updated annually and hosted on MAGICapp, a platform that aims to integrate guidelines into EMRs. Four new recommendations were added and twelve were removed. The most consequential changes are in pharmacotherapy, psychotherapy, and safety monitoring.
Pharmacotherapy: The Monotherapy Dogma Falls
The most striking change is the downgrade of antipsychotic monotherapy from a strong recommendation (Grade A) to a moderate one (Grade B). The previous preference for monotherapy was based almost entirely on registration trials, which by design tested single agents. New observational data show that some patients on antipsychotic combinations do at least as well — without higher complication rates — and randomized trials of all relevant combinations are not feasible.
(Dr. Aiken’s note: I question this. In a large controlled trial of people with schizophrenia in long-term hospital care, those randomized to reduce polypharmacy had better outcomes — both in psychotic symptoms and side effects. That’s a higher level of evidence than observational).
- Clozapine still top choice for treatment-resistant schizophrenia, with stronger recommendations to monitor serum levels.
- If clozapine isn’t possible, tolerated, or accepted, a combination of up to two antipsychotics is now explicitly permitted (Dr. Aiken’s note: aripiprazole is a promising combination, and lowers prolactin).
- Cariprazine added as option for negative symptoms (it is the only antipsychotic with evidence to improve these directly).
Safety Monitoring: A Lower Bar for Action
The definition of significant weight gain lowered from 7% to 3% body weight gain. Once that threshold is crossed, intervention is required.
- Metformin is a strong recommendation (works better as early intervention)
- Topiramate removed due to weaker evidence and safety risks (ocular complications, metabolic effects, neuropsychiatric risks, and fetal toxicity).
- GLP-1 receptor agonists are options, but were deferred in these guidelines pending future research (which has been coming in, so far positive results for safety and efficacy)
Clozapine monitoring expanded
clozapine-associated myocarditis, and new guidance on pneumonia risk.
- For clozapine-associated myocarditis, the combined elevation of CRP (>100 mg/L) and troponin (>2× upper limit of normal) has very high sensitivity for clozapine-induced myocarditis. The guideline recommends this monitoring in the first 4 weeks of treatment, when 75% of myocarditis cases occur.
- New warnings on clozapine-associated pneumonia
- Dr. Aiken’s note: Clozapine-associated constipation and small bowel obstruction is another new risk to watch for
Psychotherapy: Long-Overdue Upgrades
Several psychotherapeutic approaches were elevated based on new evidence:
- Metacognitive Training upgraded from Grade B to Grade A — making it the same tier as cognitive remediation, which has long been strongly recommended.
- Systemic Therapy upgraded from the lowest grade (0) to Grade B
- Exercise interventions upgraded from Grade B to Grade A (strong recommendation).
- Occupational therapy upgraded from Grade 0 to Grade B.
- Psychoeducation was split into two recommendations, with stronger evidence for family-inclusive psychoeducation.
Four new recommendations were added:
- Digital and technology-assisted interventions — including AVATAR therapy for auditory hallucinations — as part of a multimodal treatment plan (weak recommendation, 92% consensus)
- Mindfulness-based therapy for positive symptoms (strong recommendation, 97% consensus)
- Acceptance and Commitment Therapy (ACT) for schizophrenia (open recommendation, 96% consensus)
- Trauma-focused psychotherapy (Prolonged Exposure or EMDR) for comorbid PTSD (weak recommendation, 100% consensus)
Peolple at High Risk for Psychosis
Cognitive Behavioral Therapy (CBT) for adolescents and young adults at elevated psychosis risk was downgraded from Grade A to Grade B, based on a network meta-analysis that found no significant benefit — though the guideline group noted methodological limitations (small number of studies, wide confidence intervals).
Antipsychotics should not be used prophylactically in at-risk individuals (strong recommendation). If attenuated psychotic symptoms worsen despite CBT, low-dose second-generation antipsychotics may be used short-term as an off-label option after careful risk-benefit assessment.
Practice Implications
The full guideline is available in the MAGICapp digital platform (https://app.magicapp.org/#/guideline/jlYvkL). It is in German, and I have based this summary on an computerized translation.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
What’s Your Take? Share in Comments
- How do you find effective psychotherapy services for schizophrenia?
- What have you seen with GLP-1 agonists in schizophrenia?
- Now that the FDA has removed REMs program for clozapine monitoring, how are you making sure labs get checked?
