Dear Editor

Whitaker has performed a useful service in elucidating some of the opaque techniques employed in analysing and presenting data from the influential Finnish database studies, which are frequently cited as establishing that antipsychotics reduce mortality in people with schizophrenia or psychosis (Whitaker, Reference Whitaker2020). Unfortunately, instead of responding to these issues, Tiihonen, Taipale, and Correll (Reference Tiihonen, Taipale and Correll2020) simply cite more of the same flawed studies alongside meta-analyses of short-term randomized-controlled trials that cannot possibly provide helpful data on the mortality risk with long-term antipsychotic treatment (particularly in view of the fact that these are based on trials involving people who were previously treated with antipsychotics) (Tiihonen et al., Reference Tiihonen, Taipale and Correll2020).

As Whitaker points out, the use of person-years analysis in the database studies is particularly misleading, showing lower rates of death on antipsychotics compared with not being on antipsychotics in one analysis when in fact a higher proportion of people taking antipsychotics actually died (Taipale et al., Reference Taipale, Tanskanen, Mehtala, Vattulainen, Correll and Tiihonen2020). These analyses also suffer from survivorship bias and other forms of confounding, such as the fact that people who are more adherent to any medication (including placebo) have lower mortality (Moncrieff & Steingard, Reference Moncrieff and Steingard2018). The results also produce numerous unexplained anomalies, such as the large cohort of non-users of antipsychotics in the 2009 analysis, who were older than other patients and had high mortality rates (Tiihonen et al., Reference Tiihonen, Lonnqvist, Wahlbeck, Klaukka, Niskanen, Tanskanen and Haukka2009). The high rates of cardiovascular deaths during periods of non-use of antipsychotics in the 2020 analysis strongly suggests carry-over effects from previous antipsychotic use or high levels of confounding due to differential and uncontrolled risk factors in users v. non-users (Taipale et al., Reference Taipale, Tanskanen, Mehtala, Vattulainen, Correll and Tiihonen2020).

There is abundant evidence that antipsychotics are harmful to health, and people know this. Those who take antipsychotics can see their weight increasing and are aware of the cognitive impact of the drugs. They may know or have heard of someone who has died from sudden cardiac death, maybe at a young age. Increasingly people are aware of the evidence that antipsychotics produce brain shrinkage and tardive dyskinesia is a visible sign of the neurological damage they can produce. The promotion of flawed data, produced by associates of the pharmaceutical industry, that suggest the drugs are not so harmful after all only confirms the suspicions of sections of the service user community that professionals have their heads in the sand.

One of the findings of the database studies, along with many others, is the high proportion of people who stop taking their antipsychotic medication. This may be because people dislike taking medication in general, but research suggests it also reflects the particularly unpleasant physical, mental and behavioral alterations that antipsychotics induce, as well as people's legitimate concerns about the drugs' effects on their physical health (Thompson et al., Reference Thompson, Stansfeld, Cooper, Morant, Crellin and Moncrieff2020). As Whitaker (Reference Whitaker2020) points out, people who are treated in the current treatment paradigm may become profoundly hopeless and suicidal because of the depressing prospect of a life on antipsychotics.

None of this is to deny that antipsychotics can have useful effects in reducing psychotic symptoms and associated distress and disturbance. Doctors need to appreciate the risks people run by taking these drugs, especially for long periods of time, however, in order to support people to make their own informed decisions about their treatment.