Psychopharmacological Treatment to Reduce Suicide Risk

overdoseThe culmination of many factors—psychological, biological, social, and cultural—suicide behavior is more inclined to occur when there has been an individual, family, or socioeconomic crisis that is associated with some sort of loss or shame.[1] Psychologically, disorders such as depression, bipolar disorder, and substance abuse have the highest rates of suicide ideation and behavior.[2] Therefore, in recent years researchers have been dissecting the effects certain psychiatric treatments have on suicide risk. While historically there is little evidence that psychiatric treatments reduce the risk of suicide among patients, some medicines, including the mood-stabilizer lithium, some antipsychotics, and certain antidepressants have shown promise in more recent studies.[3] Professor of Suicidology and Assistant Professor of Psychiatry at the II Medical School of Sapienza University of Rome, Maurizio Pompili, M.D., Ph.D. and Assistant Clinical Professor of Psychiatry at Harvard Medical School Mark Goldblatt, M.D. review the current psychopharmacological interventions that have shown suicide prevention in patients with psychiatric illness in their article “Psychopharmacological Treatment to Reduce Suicide Risk: A Brief Review of Available Medications.”

Clozapine, an antipsychotic used to treat schizophrenia, was the first FDA-approved medicine with an anti-suicide indication.1 It’s approval in 2003 was based upon the International Suicide Prevention Trial which compared clozapine with olanzapine in patients who were at high risk of suicide and diagnosed with schizophrenia and schizoaffective disorder.[4] Results showed that suicidal behavior—including suicide attempts, hospitalizations, and rescue interventions—was significantly lower in patients who were treated with clozapine.1 However, other evidence states that olanzapine may reduce suicidal ideation if given in combination with a mood-stabilizing medicine for patients with bipolar I disorder mixed episode.[5] Another antipsychotic that may have promise in treating suicide behavior for patients with bipolar depression is quetiapine, when given between 300 and 600 mg per day.[6]

Kay Redfield Jamison, Ph.D. said in 1986 that “one of the most interesting questions in preventative medicine today is the impact of lithium on suicide rates.”[7] While there was no systematic information available at the time as to exactly how the medicine worked on aiding in the prevention of suicide, a decade later it began to appear.[8] A recent analysis of long-term lithium treatment for bipolar disorder and mixed major mood disorders showed an approximate 80 percent reduction in risk of suicide attempts and completed suicides.[9] Also, the lethality of suicide behavior was reduced.1

Whether or not antidepressants decrease suicidal behavior is questionable. Most data shows that SSRIs are associated with a reduced risk of suicide in adults with depression and an increased risk of suicide in adolescents with depression.[10] However, a recent study found that only 1.6 percent of adolescents who had shown suicidal behavior had taken SSRIs—most adolescents who died by suicide were not taking any antidepressants at the time of their death.[11] Therefore, the topic remains controversial. On the other hand, patients who decide to interrupt or discontinue their treatment without consulting their prescribing doctor, put themselves at risk for suicidal ideation and behavior relapse.1 While the discontinuation may be due to uncomfortable adverse effects, the risks associated with coming off a medicine may well include increased suicide behavior,[12] especially if the medicines taken have shorter half-lives.[13]

Antiepileptic medicines may possibly be associated with suicidal thoughts and behaviors. However, recent studies have reported inconsistent findings in regards to suicide risk due to taking specific antiepileptic drugs (AEDs). While patients with epilepsy may have a higher risk of suicide, many also have comorbid psychiatric conditions that may also cause the risk to increase.[14] Therefore, it is important for researchers to determine whether or not the suicide risk associated with taking anticonvulsant medicines and benzodiazepines will carry over to other psychiatric patients, as usually these drugs are used to treat a wide variety of psychiatric disorders.[15] While two studies[16],[17] have examined the associations between AEDs and suicide risks, both came up with inconclusive results. Other examinations of the AEDs levetiracetam, lamotrigine, and topiramate have shown inconsistent rankings of risk of suicide, but the drugs were found to be among the top three AEDs with the highest observed suicide risks in two of the five analyses.1 However, levetiracetam was among the top three in all five of the studies.1

Pompili and Goldblatt state that treatment of the underlying psychiatric illness in the most effective use of medicine in suicidal patients. There are some medicines that may prevent suicidal ideation and behavior; however, there are limited studies that provide sufficient information.1 While clozapine has shown to be effective at reducing suicide behavior in patients with schizophrenia, olanzapine and quetiapine appear to be promising medicines as well.1 Lithium is a trusted and effective medicine for decreasing suicidal behavior in patients with bipolar disorder, as it has for years.1 On the other hand, SSRIs are useful for the treatment of depression and possibly suicidal behavior in adults, yet their use in adolescents is controversial.1 Also, additional research on any AEDs is needed to gauge their overall safety.1

[1] Pompili, M. and Goldblatt, M.J. (2012, April 2). Psychopharmacological Treatment to Reduce Suicide Risk: A Brief Review of Available Medications. Psychiatric Times. Retrieved from: http://www.psychiatrictimes.com/display/article/10168/2053799

[2] Barraclough B, Bunch J, Nelson B, Sainsbury P. A hundred cases of suicide: clinical aspects. Br J Psychiatry. 1974;125:355-373.

[3] Angst J, Angst F, Gerber-Werder R, Gamma A. Suicide in 406 mood-disorder patients with and without long-term medication: 40 to 44 years follow-up. Arch Suicide Res. 2005;9:279-300.

[4] 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.

[5] Houston JP, Ahl J, Meyers AL, et al. Reduced suicidal ideation in bipolar I disorder mixed-episode patients in a placebo-controlled trial of olazapine combined with lithium or divalproex. J Clin Psychiatry. 2006;67:1246-1252.

[6] Thase ME, Macfadden W, Weisler RH, et al; BOLDER II Study Group. Efficacy of quetiapine monotherapy in bipolar I and II depression: a double-blind, placebo-controlled study (the BOLDER II study) [published correction appears in J Clin Psychopharmacol. 2007;27:51]. J Clin Psychopharmacol. 2006;26:600-609.

[7] Jamison KR. Suicide and bipolar disorders. Ann N Y Acad Sci. 1986;487:301-315.

[8] Baldessarini RJ, Tondo L, Hennen J. Effects of Lithium treatment and its discontinuation on suicidal behavior in bipolar manic-depressive disorders. J Clin Psychiatry. 1999;60(suppl 2):77-84.

[9] Baldessarini RJ, Tondo L, Davis P, et al. Decreased risk of suicides and attempts during long-term lithium treatment: a meta-analytic review [published correction appears in Bipolar Disord. 2007;9:314]. Bipolar Disord. 2006;8(5, pt 2):625-639.

[10] Barbui C, Esposito E, Cipriani A. Selective serotonin reuptake inhibitors and risk of suicide: a systematic review of observational studies. CMAJ. 2009;180:291-297.

[11] Dudley M, Goldney R, Hadzi-Pavlovic D. Are adolescents dying by suicide taking SSRI antidepressants? A review of observational studies. Australas Psychiatry. 2010;18:242-245.

[12] Valuck RJ, Orton HD, Libby AM. Antidepressant discontinuation and risk of suicide attempt: a retrospective, nested case-control study. J Clin Psychiatry. 2009;70:1069-1077.

[13] Shelton RC. The nature of the discontinuation syndrome associated with antidepressant drugs. J Clin Psychiatry. 2006;67(suppl 4):3-7.

[14] Hesdorffer DC, Kanner AM. The FDA alert on suicidality and antiepileptic drugs: fire or false alarm? Epilepsia. 2009;50:978-986.

[15] Pompili M, Tatarelli R, Girardi P, et al. Suicide risk during anticonvulsant treatment. Pharmacoepidemiol Drug Saf. 2010;19:525-528.

[16] Gibbons RD, Hur K, Brown CH, Mann JJ. Relationship between antiepileptic drugs and suicide attempts in patients with bipolar disorder. Arch Gen Psychiatry. 2009;66:1354-1360.

[17] Arana A, Wentworth CE, Ayuso-Mateos JL, Arellano FM. Suicide-related events in patients treated with antiepileptic drugs. N Engl J Med. 2010;363:542-551.

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