Sweden, 29,823 people with schizophrenia: about half the rehospitalization risk on clozapine or a long-acting injection
Each patient was compared with themselves, on and off the drug. Rehospitalization hazard ratios against no antipsychotic: clozapine 0.53, long-acting paliperidone 0.51, oral quetiapine 0.91.
Reasonable evidence with real limitations. how we score evidence
Caveat on this rating: Observational. Within-individual design removes stable differences between people but not the fact that stopping a drug and relapsing can share a cause. Industry-employed co-authors and the ranking of the sponsor's product first warrant the usual caution.
The obvious flaw in comparing people on a drug with people off it is that they are different people. This study compared each person with themselves.
Significant findings
Tiihonen and colleagues (JAMA Psychiatry, 2017) linked Swedish national registers for "all patients in Sweden with a schizophrenia diagnosis who were 16 to 64 years of age in 2006 (29 823 patients", followed to 2013. "Within-individual analyses were used for primary analyses, in which each individual was used as his or her own control to eliminate selection bias."
"During follow-up, 13 042 of 29 823 patients (43.7%) were rehospitalized". Against periods of no antipsychotic use, "the risk of psychiatric rehospitalization was the lowest during monotherapy with once-monthly long-acting injectable paliperidone (hazard ratio [HR], 0.51; 95% CI, 0.41-0.64), long-acting injectable zuclopenthixol (HR, 0.53", "clozapine (HR, 0.53; 95% CI, 0.48-0.58)". The weakest were oral: "quetiapine (HR, 0.91; 95% CI, 0.83-1.00)". "Long-acting injectable antipsychotic medications were associated with substantially lower risk of rehospitalization compared with equivalent oral formulations (HR, 0.78".
Worth asking
This is the strongest evidence against the idea that these drugs put people in hospital: within the same person, time on clozapine or an injection meant about half the admissions. Two cautions belong beside it. Co-authors included employees of Janssen-Cilag, which makes the injectable paliperidone that ranked first, and the lead author lists consulting and lecture fees from most makers of antipsychotics. And people tend to stop medication when they are already getting worse, which makes off-drug periods look bad even with each person as their own control. Never stop an antipsychotic on your own.
Source
Real-World Effectiveness of Antipsychotic Treatments in a Nationwide Cohort of 29 823 Patients With Schizophrenia — Tiihonen J, Mittendorfer-Rutz E, Majak M, Mehtala J, Hoti F, Jedenius E, Enkusson D, Leval A, Sermon J, Tanskanen A, Taipale H (2017)
Top-tier peer-reviewed journal
Read the source: https://doi.org/10.1001/jamapsychiatry.2017.1322
DOI: 10.1001/jamapsychiatry.2017.1322
How this was scored
- Study design
- Cohort study
- Funding
- Funding not disclosed
- Published in
- Top-tier peer-reviewed journal
- Sample size
- 29,823
- Preregistered
- not recorded
- Conflicts disclosed
- Yes
- Independent of proponent
- not recorded
- Retracted
- No
Read the full scoring rubric, including what it can't tell you.
Published September 21, 2026.
Questions
How strong is the evidence behind this?
veisund rates this source "moderate evidence". Reasonable evidence with real limitations. It scores 62 out of 100 on our published rubric. One caveat travels with that badge: Observational. Within-individual design removes stable differences between people but not the fact that stopping a drug and relapsing can share a cause. Industry-employed co-authors and the ranking of the sponsor's product first warrant the usual caution. The score is calculated from recorded facts about the source — study design, funding, publication venue, sample size, preregistration — not typed in by an editor.
What is the source for this?
Real-World Effectiveness of Antipsychotic Treatments in a Nationwide Cohort of 29 823 Patients With Schizophrenia — Tiihonen J, Mittendorfer-Rutz E, Majak M, Mehtala J, Hoti F, Jedenius E, Enkusson D, Leval A, Sermon J, Tanskanen A, Taipale H (2017). Published in: Top-tier peer-reviewed journal. DOI: 10.1001/jamapsychiatry.2017.1322. The full source is linked on this page so you can read it yourself.
Who paid for this research, and does that matter?
Study design: Cohort study. Funding: Funding not disclosed. Independence from the proponent is not recorded. Industry sponsorship is one of the most reliably measured biases in medicine, which is why funding carries real weight in the score rather than sitting in a footnote.
Is this medical advice?
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.