How Antipsychotic Medication May Save Lives

Psychiatric TimesVol 33 No 6
Volume 33
Issue 6

For patients suffering the chronic, debilitating symptoms of schizophrenia, antipsychotic medication is a critical component of treatment-and may literally be life-saving.

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One way anti-psychiatry groups trivialize psychosis and marginalize psychiatry is by emphasizing the adverse effects of antipsychotic medications while denying or minimizing their benefits.1 To be sure, the well-recognized metabolic, neurological, and cardiovascular risks associated with many antipsychotic medications must be taken very seriously. Moreover, antipsychotics (APs) are often used when they are not needed; eg, for the treatment of anxiety disorders2; for “agitation” in nursing home patients; and for “acting out” in adolescent populations. (I spent many years as a psychopharmacology consultant trying to get doctors to reduce their over-reliance on antipsychotics.) On the other hand, there is convincing evidence that in patients with chronic schizophrenia, APs play a crucial role in maintaining remission, averting relapse, improving quality of life, and-importantly-reducing overall mortality.3-5

But even many psychiatrists may not realize that APs reduce the risk of suicide in patients with schizophrenia.

To back up a bit: an estimated 20% to 40% of those with schizophrenia attempt6-and 5% complete-suicide7-a risk at least 10 times that of the general public. Suicides are concentrated early in the illness course and are associated with a number of risk factors, ie:

“Risk factors with a strong association with later suicide included being young, male, and with a high level of education. Illness-related risk factors were important predictors, with number of prior suicide attempts, depressive symptoms, active hallucinations and delusions, and the presence of insight all having a strong evidential basis. A family history of suicide and co-morbid substance misuse were also positively associated with later suicide. The only consistent protective factor for suicide was delivery of and adherence to effective treatment.”8 [italics added].

This last point, of course, is crucial. Indeed, the authors add that,

“. . . efforts at prevention should focus on optimizing adherence to medication, and possible earlier use of clozapine, as the only antipsychotic medication with demonstrated efficacy . . . for the management of suicidality in schizophrenia.”8

Indeed, the first FDA-approved medication with an anti-suicide indication was clozapine for schizophrenia. The regulatory approval in 2003 was largely based on the International Suicide Prevention Trial (InterSePT), a randomized trial that compared clozapine with olanzapine in patients with schizophrenia and schizoaffective disorder who were at high risk for suicide.9 Suicidal behavior (measured by suicide attempts, hospitalizations, and rescue interventions) was significantly decreased in patients treated with clozapine, which is associated with a substantially lower risk of suicide than any other antipsychotic.10

There is little question that, for patients suffering the chronic, debilitating symptoms of schizophrenia, antipsychotic medication is a critical component of treatment-and may literally be life-saving.

But while clozapine provides the best evidence of anti-suicidal properties in schizophrenia, there is accumulating evidence that antipsychotic medication in general is associated with decreased risk of suicide in this population. For example, Tiihonen and colleagues11 performed an observational study of antipsychotic treatment in patients with schizophrenia and schizoaffective disorder (N = 2230, average length of follow-up =3.6 years). Excess mortality was seen mostly in patients not taking antipsychotic drugs, for whom the risk of suicide was high. There were 26 suicides in patients not taking antipsychotics compared with 1 in patients taking medication (adjusted relative risk 37.4).11

Consistent with these data, Herings and Erkins12 studied drug refill patterns in patients believed to have schizophrenia. They found a 4-fold increased risk for attempting suicide among patients who interrupted their use of olanzapine or risperidone for at least 30 days.

Recently, Tiihonen and associates13 carried out a large observational study (N = 21,492) of patients with schizophrenia. The study found that antipsychotic use was associated with substantially lower overall mortality and very significantly reduced rates of completed suicide across the entire dosage range (low to moderate to high) when compared with no antipsychotic drug use (10% of the entire sample). Maximum anti-suicide benefit was seen with the higher antipsychotic doses.

Analysis of this study by Dr. Bernard Carroll shows that for the group with no antipsychotic exposure, the suicide rate was 183 per 100,000 person years. In the medium-plus-high dosage AP groups, the combined rate fell to 129 suicides per 100,000 person years-roughly a 30% reduction from the no-medication group (B. Carroll MD, personal communication, 3/27/16). Moreover, if we make the reasonable assumption that patients receiving the highest doses of AP were probably the most severely impaired-and thus, at highest risk for suicide-these findings are all the more impressive.

Of course, in non-randomized, observational studies, there is always the potential for “selection bias” and/or “reversed causality.” For example, it is possible that patients who become suicidal-for whatever reason-stop taking their antipsychotic, rather than becoming suicidal because they stopped the medication. However, the apparent dose-response seen in the Tiihonen et al data-ie, suicide rates declined as medication dose increased-plausibly suggests that medication was actually bringing down suicide rates.14

Multi-modal treatment

It would be incorrect to infer from this brief review that the optimal treatment of schizophrenia is simply a matter of giving patients antipsychotic medication. Persons with schizophrenia have lives beyond their symptoms. They often require and benefit from a range of adjunctive psychosocial services, including assertive community treatment, supported employment, cognitive behavioral therapy, family-based services, skills training, psychosocial interventions for alcohol and substance use disorders, and psychosocial interventions for weight management.15

But there is little question that, for patients suffering the chronic, debilitating symptoms of schizophrenia, antipsychotic medication is a critical component of treatment-and may literally be life-saving.

Acknowledgments: I would like to thank Drs. Barney Carroll and Jari Tiihonen for their helpful assistance with this piece.

This article was originally posted on 4/18/2016 and has since been updated.

Note to readers: As with all of our content, the opinions expressed in this commentary are solely those of the author. Comments not followed by full names and academic titles will either be removed or heavily monitored. –Psychiatric Times


Dr Pies is Professor in the psychiatry departments of SUNY Upstate Medical University, Syracuse, NY, and Tufts University School of Medicine, Boston, and Editor in Chief Emeritus of Psychiatric Times.


1. Pies R. Trivializing the suffering of psychosis. Psychiatric Times. December 22, 2014.

2. Pies R. Should psychiatrists use atypical antipsychotics to treat nonpsychotic anxiety? Psychiatry (Edgmont). 2009;6(6):29-37.

3. Pies R. Long-term antipsychotic treatment: effective and often necessary, with caveats. Psychiatric Times. February 22, 2016.

4. Leucht S, Tardy M, Komossa K, et al. Maintenance treatment with antipsychotic drugs for schizophrenia. Cochrane Database Syst Rev. 2012 May 16;5:CD008016.

5. Ran MS, Weng X, Chan CL, et al. Different outcomes of never-treated and treated patients with schizophrenia: 14-year follow-up study in rural China. Br J Psychiatry. 2015;207:495–500.

6. Schizophrenia and suicide.WebMD.

7. Palmer BA, Pankratz VS, Bostwick JM. The lifetime risk of suicide in schizophrenia: a reexamination. Arch Gen Psychiatry. 2005;62:247-253.

8. Hor K, Taylor M. Suicide and schizophrenia: a systematic review of rates and risk factors. J Psychopharmacol. 2010;24(Suppl 4):81–90.

9. Meltzer HY, Alphs L, Green AI, et al. International Suicide Prevention Trial Study Group. Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT) [published correction appears in Arch Gen Psychiatry. 2003;60:735]. Arch Gen Psychiatry. 2003;60:82-91.

10.Tiihonen J, Lönnqvist J, Wahlbeck K, et al. 11-year follow-up of mortality in patients with schizophrenia:a population-based cohort study (FIN11 study) Lancet. 2009;374:620–627.

11.Tiihonen J, Wahlbeck K, Lönnqvist J, et al. Effectiveness of antipsychotic treatments in a nationwide cohort of patients in community care after first hospitalisation due to schizophrenia and schizoaffective disorder: observational follow-up study. BMJ. 2006;333(7561):224.

12. Herings RM, Erkens JA. Increased suicide attempt rate among patients interrupting use of atypical antipsychotics. Pharmacoepidemiol Drug Saf. 2003;12:423-424.

13. Tiihonen J, Mittendorfer-Rutz E, Torniainen M, et al. Mortality and cumulative exposure to antipsychotics, antidepressants, and benzodiazepines in patients with schizophrenia: an observational follow-up study. Am J Psychiatry. 2015;Dec 7.

14. Hill AB. The Environment and Disease: Association or Causation? Proc R Soc Med. 1965;58:295-300.

15. Dixon LB, Dickerson F, Bellack AS, et al. Schizophrenia Patient Outcomes Research Team (PORT). The 2009 schizophrenia PORT psychosocial treatment recommendations and summary statements. Schizophr Bull. 2010;36:48-70.

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