Psychiatric pharmacoepidemiology

The research in psychiatric pharmacoepidemiology at the Division of Insurance medicine is mainly carried out in the Research group MENTE. The research uses large-scale Nordic nationwide register data, including data from the IMAS project within the national infrastructure REWHARD to generate real-world evidence regarding treatment with psychiatric medication on severe mental disorders.

The overarching goal is to improve clinical practice and patient outcomes by studying medication effectiveness, safety, and optimal use in real-world settings, where patients often differ from randomized controlled trial (RCT) populations. The research frequently employs advanced methods like within-individual designs (to control for confounding), the PRE2DUP method (for accurate drug exposure periods from dispensing data), and population-based cohorts.

Core Research Themes

• Antipsychotic Effectiveness and Relapse Prevention in Schizophrenia and Related Psychoses Comparative real-world effectiveness of different antipsychotics (including clozapine, long-acting injectables/LAIs, dosing strategies, monotherapy vs. polypharmacy, and augmentation). Emphasis on first-episode schizophrenia, relapse after initial treatment failure, and cannabis/substance-induced psychosis. Recent work supports earlier clozapine use and optimized dosing for better outcomes.
• Safety Profiles and Long-Term Risks Drug-specific adverse outcomes, such as breast cancer risk linked to prolactin-elevating antipsychotics in women with schizophrenia, pneumonia risk, physical morbidity/mortality, and metabolic/endocrine effects. Broader studies on mortality, hospitalizations, and physical health comorbidities in severe mental illness.
• Real-World Generalizability and Patient Representation Outcomes in everyday practice patients (often ineligible for RCTs due to comorbidities, etc.), highlighting differences from trial populations and the value of register-based evidence. Extended to major depression and other conditions.
• Drug Repurposing and Broader Pharmacotherapies Exploring medications like GLP-1 receptor agonists (e.g., semaglutide, liraglutide) for alcohol use disorder and related mental health applications. Also covers ADHD medications in bipolar/schizophrenia, mood stabilizers, and other adjuncts.
• Special Populations and Comorbidities Substance use disorders (especially cannabis) co-occurring with psychosis; migrant/refugee populations; women's health; bipolar disorder; employment/sickness absence; and prediction models (e.g., machine learning for relapse or mortality risk).
• Methodological Advancements Developing and validating tools for pharmacoepidemiology (e.g., PRE2DUP-R open-source method) and clinical prediction models to support personalized treatment planning.

Project members

Heidi Taipale

Jari Tiihonen

Ellenor Mittendorfer-Rutz

Antti Mustonen

Antti Tanskanen

Johannes Lieslehto

Publications

Examples of the 10 most influential publications 

Tiihonen J, Mittendorfer-Rutz E, Majak M, Mehtälä J, Hoti F, Mehtälä J, Hoti F, Jedenius E, Enkusson D, Leval A, Sermon J, Tanskanen A, Taipale H. Real-world effectiveness of antipsychotic treatments in a nationwide cohort of 29 823 patients with schizophrenia. JAMA Psychiatry 2017;74(7):686-693.

• Journal: JAMA Psychiatry (2017)
• Summary: Nationwide cohort (≈30,000 patients) comparing effectiveness of different antipsychotics. Found clozapine and long‑acting injectables most effective in preventing relapse.
• Impact: ~800 citations

Taipale H, Tanskanen A, Mehtälä J, Vattulainen P, Correll CU, Tiihonen J. 20-year follow-up study of physical morbidity and mortality in relationship to antipsychotic treatment in a nationwide cohort of 62,250 patients with schizophrenia (FIN20). World Psychiatry 2020;19(1):61-68

• Journal: World Psychiatry (2020)
• Summary: 20‑year follow‑up (≈62,000 patients) linking antipsychotic use with reduced mortality risk, especially with continuous treatment.
• Impact: ~490 citations 

Tiihonen J, Taipale H, Mehtälä J, Vattulainen P, Correll CU, Tanskanen A. Association of Antipsychotic Polypharmacy vs Monotherapy With Psychiatric Rehospitalization Among Adults With Schizophrenia. JAMA Psychiatry. 2019;76(5):499-507.

• Journal: JAMA Psychiatry (2019)
• Summary: Within‑individual design showing polypharmacy can reduce rehospitalisation risk compared with monotherapy under real‑world conditions.
• Impact: ~380 citations 

Taipale H, Mittendorfer-Rutz E, Alexanderson K, Majak M, Mehtälä J, Hoti F, Jedenius E, Enkusson D, Leval A, Sermon J, Tanskanen A, Tiihonen J. Antipsychotics and mortality in a nationwide cohort of 29,823 patients with schizophrenia. Schizophrenia Research 2018; 197:274-280. 

• Journal: Schizophrenia Research (2018)
• Summary: Demonstrated lower mortality among treated patients vs untreated, reinforcing importance of adherence.
• Impact: ~350 citations

Tiihonen J, Tanskanen A, Taipale H. 20-year nationwide follow-up study on discontinuation of antipsychotic treatment in first-episode schizophrenia. American Journal of Psychiatry 2018; 175(8):707-795

• Journal: American Journal of Psychiatry (2018)
• Summary: Long‑term follow‑up showing high discontinuation rates and increased relapse risk, underscoring need for sustained treatment.
• Impact: ~260+ citations 

Pirkis J, John A, Shin S, DelPozo-Banos M, Arya V, Analuisa-Aguilar P et al. Suicide trends in the early months of the COVID-19 pandemic: an interrupted time-series analysis of preliminary data from 21 countries. Lancet Psychiatry. 2021 Jul;8(7):579-588. 

• Journal: The Lancet Psychiatry (2021)
• Summary: Interrupted time‑series (21 countries) showing no universal early increase in suicide rates, contradicting early concerns.
• Impact: ~900+ citations 

Hirvikoski T, Mittendorfer-Rutz E, Boman M, Larsson H, Lichtenstein P, Bölte S. Premature mortality in autism spectrum disorder. Br J Psychiatry. 2016 Mar;208(3):232-8. 

• Journal: British Journal of Psychiatry (2016)
• Summary: Large population study showing substantially elevated premature mortality in autism, especially among women.
• Impact: ~1,400 citations 

Correll CU, Solmi M, Croatto G, Schneider LK, Rohani-Montez SC, Fairley L, Smith N, Bitter I, Gorwood P, Taipale H, Tiihonen J. Mortality in people with schizophrenia: a systematic review and meta-analysis of relative risk and aggravating or attenuating factors. World Psychiatry. 2022 Jun;21(2):248-271.

• Journal: World Psychiatry (2022)
• Summary: Comprehensive meta‑analysis confirming marked excess mortality and key risk modifiers (e.g., comorbidity, lifestyle).
• Impact: ~700+ citations 

Puranen A, Koponen M, Lähteenvuo M, Tanskanen A, Tiihonen J, Taipale H. Real-world effectiveness of antidepressant use in persons with schizophrenia: within-individual study of 61,889 subjects. Schizophrenia (Heidelb). 2023 May 26;9(1):34.

• Journal: Schizophrenia (Nature portfolio, 2023)
• Summary: Nationwide cohort (~62,000 patients) showing antidepressants modestly reduce relapse and mortality risk, with acceptable safety

Taipale H, Siskind D, Tanskanen A, Mittendorfer-Rutz E, Correll CU, Tiihonen J. Real-world effectiveness of clozapine augmentation with antidepressants: within-subject data evidence from two European nationwide cohorts. Lancet Psychiatry. 2025 Aug;12(8):568-578.

• Journal: The Lancet Psychiatry (2025)
• Summary: Large Nordic cohorts showing certain antidepressants (e.g., sertraline, duloxetine) reduce relapse risk when added to clozapine