Antipsychotic - Efficacy

Efficacy

There have been a large number of studies of the efficacy of typical antipsychotics, and an increasing number on the more recent atypical antipsychotics.

The American Psychiatric Association and the UK National Institute for Health and Clinical Excellence recommend antipsychotics for managing acute psychotic episodes in schizophrenia or bipolar disorder, and as a longer-term maintenance treatment for reducing the likelihood of further episodes. They state that response to any given antipsychotic can be variable so that trials may be necessary, and that lower doses are to be preferred where possible. A number of studies have looked at levels of "compliance" or "adherence" with antipsychotic regimes and found that discontinuation (stopping taking them) by patients is associated with higher rates of relapse, including hospitalization.

Nevertheless, a 2009 systematic review and meta-analysis of trials in people diagnosed with schizophrenia found that less than half (41%) showed any therapeutic response to an antipsychotic, compared to 24% on placebo, and that there was a decline in treatment response over time, and possibly a bias in which trial results were published. In addition, a 2010 Cochrane Collaboration review of trials of Risperidone, one of the biggest selling antipsychotics and the first of the new generation to become available in generic form, found only marginal benefit compared with placebo and that, despite its widespread use, evidence remains limited, poorly reported and probably biased in favor of risperidone due to pharmaceutical company funding of trials. Another Cochrane review in 2009, of bipolar disorder, found the efficacy and risk/benefit ratio better for the traditional mood stabilizer lithium than for the antipsychotic Olanzapine as a first line maintenance treatment.

Antipsychotic polypharmacy (prescribing two or more antipsychotics at the same time for an individual) is said to be a common practice but not necessarily evidence-based or recommended, and there have been initiatives to curtail it. Similarly, the use of excessively high doses (often the result of polypharmacy) continues despite clinical guidelines and evidence indicating that it is usually no more effective but is usually more harmful.

A review by the US Agency for Healthcare Research and Quality found that much of the evidence for the off-label use of antipsychotics (for example, for depression, dementia, OCD, PTSD, Personality Disorders, Tourette's) was of insufficient scientific quality to support such use, especially as there was strong evidence of increased risks of stroke, tremors, significant weight gain, sedation, and gastrointestinal problems. A UK review of unlicensed usage in children and adolescents reported a similar mixture of findings and concerns.

Aggressive challenging behavior in adults with intellectual disability is often treated with antipsychotic drugs despite lack of an evidence base. A recent randomized controlled trial, however, found no benefit over placebo and recommended that the use of antipsychotics in this way should no longer be regarded as an acceptable routine treatment.

A 2006 Cochrane Collaboration review of controlled trials of antipsychotics in old age dementia reported that one or two of the drugs showed a modest benefit compared to placebo in managing aggression or psychosis, but that this was combined with a significant increase in serious adverse events. They concluded that this confirms that antipsychotics should not be used routinely to treat dementia patients with aggression or psychosis, but may be an option in the minority of cases where there is severe distress or risk of physical harm to others.

Some doubts have been raised about the long-term effectiveness of antipsychotics for schizophrenia, in part because two large international World Health Organization studies found individuals diagnosed with schizophrenia tend to have better long-term outcomes in developing countries (where there is lower availability and use of antipsychotics and mental health problems are treated with more informal, community-led methods only) than in developed countries.

Some argue that the evidence for antipsychotics from discontinuation-relapse studies may be flawed, because they do not take into account that antipsychotics may sensitize the brain and provoke psychosis if discontinued, which may then be wrongly interpreted as a relapse of the original condition. Evidence from comparison studies indicates that at least some individuals with schizophrenia recover from psychosis without taking antipsychotics, and may do better in the long term than those that do take antipsychotics. Some argue that, overall, the evidence suggests that antipsychotics only help if they are used selectively and are gradually withdrawn as soon as possible and have referred to the "Myth of the antipsychotic".

A review of the methods used in trials of antipsychotics, despite stating that the overall quality is "rather good," reported issues with the selection of participants (including that in schizophrenia trials up to 90% of people who are generally suitable do not meet the elaborate inclusion and exclusion criteria, and that negative symptoms have not been properly assessed despite companies marketing the newer antipsychotics for these); issues with the design of trials (including pharmaceutical company funding of most of them, and inadequate experimental "blinding" so that trial participants could sometimes tell whether they were on placebo or not); and issues with the assessment of outcomes (including the use of a minimal reduction in scores to show "response," lack of assessment of quality of life or recovery, a high rate of discontinuation, selective highlighting of favorable results in the abstracts of publications, and poor reporting of side-effects).