It is widely reported that patients with schizophrenia are at increased risk of poor physical health and are dying 20 years earlier than the general population (see People with schizophrenia are significantly more likely to die from heart disease and cancer and National Schizophrenia Audit calls for improved monitoring of physical health in people with schizophrenia). A number of factors may influence this: stigma, poorer access to healthcare, diagnostic overshadowing, lifestyle factors and the adverse effects of psychotropic medications.

This paper by Correll and colleagues (Correll et al, 2015) aims to summarise physical health risks associated with various drug treatments (antipsychotics, antidepressants and mood stabilisers) for people with schizophrenia, depression and bipolar disorder.

Methods

This is an update of a previous systematic review published in 2011. An additional search of MESH terms was conducted via Medline from 2009 to 2014, restricted to English language only. The researchers aimed to include only systematic reviews or meta-analysis, although did include individual studies for some diseases. There was no discussion of critical appraisal or selection techniques for studies identified. The search identified 13,477 hits which appears to include 2,429 reviews.

Results

• The risk for weight gain is greatest in the early weeks of treatment, and is greater for second generation antipsychotics (i.e. clozapine, olanzapine). Antidepressants, mood stabilisers and some first generation antipsychotics can also contribute to weight gain.
• The risk for diabetes mellitus (type 2) is greater in those with schizophrenia and bipolar disorder and seems to be linked to antipsychotic treatment. This may or may not be linked to weight gain. There seems to be some risk of developing diabetes associated with mood stabilisers and antidepressants although this is less clear.
• The risk for coronary heart disease and stroke are clearly higher in people with schizophrenia, but how antipsychotic treatment influences this is less well understood. Whilst antidepressants (particularly tricyclics) risks are clearly known about, the role of mood stabilisers is less well understood.
• The risk of sudden cardiac death is higher for those treated with antipsychotic and antidepressant medications; this appears to be dose related. The importance of ECG (electrocardiogram) monitoring is therefore essential to identify changes to heart rates and beats.
• The risk of pneumonia appears greatest when treated with clozapine (for both treatment in schizophrenia and bipolar disorder) and second generation antipsychotics. On their own, antidepressants and mood stabilisers appear to have no significant risk.
• The risk of leukocytopenia/ neutropenia (fewer of these white blood cells) and agranulocytosis (impact on immunity) is associated with antipsychotics, mood stabilisers and antidepressants. The greatest risk is associated with starting treatment with clozapine particularly for neutropenia and agranulocytosis.
• The risk of reduced bone density, osteoporosis and broken bones is higher in schizophrenia and bipolar disorders. This seems related to antipsychotics and newer antidepressants (SSRIs).
• Antidepressants and antipsychotics can reduce the seizure threshold. First generation antipsychotics are more likely to lead to movement disorders. Lithium particularly after long-term use might lead to reduced renal function.

Conclusions

The authors concluded:

In general, adverse effects on physical health are greatest with antipsychotics, followed by mood stabilisers, tricyclic antidepressants and newer antidepressants. However, effects vary greatly among individual agents, and interactions with underlying host factors are relevant. Higher dosages, polypharmacy, and the treatment of vulnerable (e.g. old or young) people seems to be associated with a greater effect on most physical diseases.

Limitations

The search was limited to English language only, and focused on MeSH terms. There was no discussion of the quality of literature included. It was not clear how the literature was synthesised together and how risk judgements were made. There is also no account of how or if the previous systematic review was integrated into this newer one. 

Overall this made for a rather frustrating read and it was difficult to critically appraise this review because the methods section was very brief. Of course this may simply be that the journal (World Psychiatry) did not have sufficient space to publish a lengthy methods section, in which case I invite the study authors to contact us and share their methods more fully, e.g.

• How many and what type of studies were included in your analysis?
• What inclusion criteria did you use?
• Who was involved in selecting studies for inclusion?
• How was study quality assessed? 
• How was the data synthesised?
• How were risk judgements made?

Discussion

Whilst psychotropic medication can help with symptoms, contribute to recovery and reduce risks such as suicide, it can clearly impact negatively on the physical health and well-being of the patient. In addition to the iatrogenic effects of psychotropic medication the health service needs to work harder at ensuring that individuals with mental health disorders have and maintain good physical health. Lia Ali’s blog and the IMPARTS team work are good example of recent initiatives to do this.

It’s incredibly important, but incredibly difficult to synthesise and summarise the vast literature on the impact of treatments for mental health disorders (antipsychotics, antidepressants and mood stabilisers) has on aspects of physical health. If nothing else I would recommend spending time exploring Table 2 of the Correll (2015) paper which provides a good summary of all of their findings across the conditions and associated treatments. Clearly the focus of future research needs to be on those physical health conditions which have been less well explored or studied for example, sudden death, sexual and reproductive health, impact on hormones and conditions which may result from this.

Links

Primary paper

Correll CU, Detraux J, De Lepeleire J, De Hert M. (2015) Effects of antipsychotics, antidepressants and mood stabilizers on risk for physical diseases in people with schizophrenia, depression and bipolar disorder (PDF). World Psychiatry. 2015 Jun;14(2):119-36. doi: 10.1002/wps.20204.

Other references

DE Hert M, Correll CU, Bobes J, Cetkovich-Bakmas M, Cohen D, Asai I, Detraux J, Gautam S, Möller HJ, Ndetei DM, Newcomer JW, Uwakwe R, Leucht S. (2011) Physical illness in patients with severe mental disorders. I. Prevalence, impact of medications and disparities in health care (PDF). World Psychiatry. 2011 Feb;10(1):52-77.