Edição No. 23 (Maio de 2006)&= nbsp; - Ano X

&nb= sp;

&nbs= p;

O= riginal Article

Neuropsychopharmacology (2006) 31, 178-181.

d= oi:10.1038/sj.npp.1300863; published online = 3 August 2005

<= o:p>

Antidepressants Reduce the Risk of Suicide among Elderly Depressed Patients

<= o:p>

Yoram Barak, Ahikam Olmer and Dov Aizenberg

Abarbanel Mental Health Center and Geha Mental Heal= th Center, Affiliated with the Sackler Faculty of Medicine, Tel-Aviv University, Bat-Yam, Israel

<= o:p>

C= orrespondence: Professor Y Barak, Abarban= el Mental Health Center, 15 KKL Street, Bat-Yam, 59100, Israel. Tel: 972 3 5552738; Fax: 972 3 5552738; E-mail: mdybarak@netvisio= n.net.il

<= o:p>

A= BSTRACT

<= o:p>

T= reatment with selective serotonin reuptake inhibitors (SSRIs) may increase the risk of impulsive acts including suicide, while data from epidemiological studies suggest that the effect of SSR= Is in the elderly may be beneficial. We aimed to evaluate the association betw= een exposure to antidepressants and suicidality in a cohort of elderly patients suffering from major depressive disorder (MDD). = This was a retrospective matched case-controlled evaluation over a 10-year perio= d. All records of admissions of patients with MDD (ICD-10) were assessed. The index group comprised all patients who had attempted suicide = in the month prior to admission. The case-controlled group was the next admiss= ion of a patient suffering from MDD, matched for sex and age who had not attempted suicide in the month prior to admission. The index group during the 10-year period (1995-2004) consisted of 101 patients suffering f= rom MDD who were hospitalized following a suicide attempt. Mean age for the gro= up was 76.5±6.6 years; there were 42 men and 59 women. The control group patients (N=3D101) were matched for age (mean 76.6±6.9 years) and se= x. The proportion of patients exposed to an antidepressant was significantly great= er in the control group, than in the group of patients who had attempted suici= de (58 vs 42%, odds ratio 1.94 (95% CI: 1.1-3.4), p=3D0.019). SSRIs were prescribed in 29% of pat= ients in the control group vs 21% of patients in the ind= ex group (p=3D0.03). It is of interest to note that concomitant prescription of benzodiazepines also conferred a protective effect. In conclusion, elderly depressed patients treated with antidepressants may be at reduced risk of a= ttempting suicide. These findings need support from prospective randomized trials.

<= o:p>

K= eywords: suicide; depression; elderly; SSRIs<= /span>

I= NTRODUCTION

<= o:p>

T= he most significant risk factors for attempted suicide include mood disorders and a history of suicide attempts. Suicide risk is assessed along a continuum from suicidal ideation alone to completed suicide. Although the incidence of sui= cide is low in the general population, it was among the leading causes of death = in the Western world in 2000. Adolescents and the elderly are particularly at = risk for suicide (Gaynes et al, 2004; Charney et al, 2003). Seniors aged 75 years and above have the highest suicide rate= s of all age groups in most industrialized countries (Waern= et al, 2003).

<= o:p>

D= espite the availability of efficacious treatments, late-life depression remains improp= erly diagnosed and inadequately treated. Antidepressants are increasingly prescr= ibed since the 1990s, yet pharmacotherapeutic treatm= ent of depression is still inadequate due to insufficient dosing and short period = of treatment (Fischer et al, 2003; Salzman et al, = 2002).

<= o:p>

T= he estimated population attributable risk for mood disorder in elderly suicide is 74%; that is, if mood disorders were elimina= ted from the population, 74% of suicides would be prevented in the elderly (Beautrais, 2002). 'Elimination' of mood disorders is possible not only by treatment of existing cases but also by primary and secondary prevention (O'Connell et al, 2004). In recent years, attempts have been made to prevent suicide in the community through various interventions= in primary care, with particular emphasis on elderly subjects since they are at high risk. One of the leading trials, known as Prevention of Suicide in Pri= mary Care Elderly: Collaborative Trial (PROSPECT), recruited 598 patients from 20 primary care practices in the USA. The PROSPECT algorithm recommended a first-line trial of a selective serotonin reuptake inhibitor (SSRI), as this reflects the reality of primary care. The intervention's effectiveness in reducing suicidal ideation reinforces its role as a preven= tion strategy to reduce risk factors for suicide in late life (Bruce et al, 2004= ). The demonstrated effect in the PROSPECT trial was already predicted by Freemantle et al (1994) concerning the population of England, as follows: 'The potential number of lives which may be saved from= a switch to the routine first line use of SSRIs is between 300 and 450 each year'. Despite the enthusiasm shown by several research groups for the use of SSRIs as potently decreasing the risk of suicide, others have reported increased impulsivity = and increased rates of suicide associated with exposure to SSRIs (Teicher et al, 1993; Donovan et al, 1999; Heal= y, 2003). In a recent review of several meta-analyses, Healy and Whitaker (200= 3) emphasized the need to identify the characteristics of patients who may be = most at risk. Thus, the present study was designed to assess the effects of expo= sure to antidepressants in elderly patients suffering from major depression¾possibly the group of patients at the highest risk of suicide.

M= ETHOD

<= o:p>

T= here are no private emergency psychiatric facilities in Israel, and all acute psychia= tric hospitalizations are regional and reported to the Ministry of Health.<= /o:p>

<= o:p>

T= he Abarbanel Mental Health Center, <= st1:City w:st=3D"on">Bat-Yam, Israel, serves a catchment area of approximately 680 000 subjects. The center is affiliated to the Sackler School of Medicine, Tel-A= viv University. There a= re 470 in-patient beds and 60 day patients, as well as a large outpatient clinic. = This is a tertiary psychiatric facility in contact with both secondary specialist clinics and primary care providers. The services for the elderly include two in-patient departments, an outpatient clinic, and outreach consultancy serv= ices for nursing homes within the catchment area.

<= o:p>

T= he present study is a retrospective analysis of all records of elderly patients suffer= ing from major affective disorder (unipolar depress= ion, MDD) admitted to our center over a period of 10 years. The center's Internal Review Board (IRB) approved this study.

<= o:p>

T= he Israeli Ministry of Health requires that there be a record of suicide attempt in th= e 4 weeks preceding the hospitalization for every admission to a psychiatric wa= rd. The records are transferred to the Ministry weekly and a copy is kept at ev= ery site. During the period January 1995 and December 2004 there were 852 admissions to our center of elderly patients who had attempted suicide prio= r to hospitalization. This data set (N=3D852) was queried for all elderly patien= ts fulfilling the following inclusion criteria: (1) ICD-10 diagnosis of depres= sive episode or recurrent depressive episode (F32 and F33 codes; all subtypes) a= nd (2) availability of treatment charts.

<= o:p>

P= atients who had fulfilled these criteria were defined as the index group (ie, elderly major depressive disorder (MDD) patients = who had attempted suicide within 1 month prior to admission). The case-controll= ed group comprised the next admission of an elderly patient suffering from MDD, with available treatment chart, matched for sex and age (within 1 year) who= had not attempted suicide within 1 month prior to hospitalization.

<= o:p>

C= omputerized index and control patient files were reviewed and the following data extrac= ted: age, sex, diagnosis subtype, suicide attempt prior to admission (index pati= ents), treatment with psychotropic medication, manner of suicide attempt (index patients), and history of prior suicide attempts.

S= tatistical Analysis

<= o:p>

D= ata were analyzed using the nonparametric sign-rank test for paired groups. This met= hod was employed due to uneven distribution of within-group differences. The t-= test and a nonparametric test were undertaken to test for differences between the evaluations for continuous variables. Examination of differences between the categorical parameters was based on the McNemar= test for dependent (matched) populations. All tests applied were two tailed, and= a p-value of 5% or less was considered statistically significant.<= /span>

<= o:p>

T= he data were analyzed using the Statistical Analysis System software, SAS Institute (1990).

R= ESULTS

<= o:p>

D= uring the study period, 205 elderly MDD were hospitalized at the Abarbanel Mental Health Center psycho-geria= tric division following a suicide attempt. Of these, 101 MDD patients fulfilled = all inclusion criteria and are the index group of the present analysis. The 104 discarded files were missing data as to the details and manner of the suici= de attempt (N=3D82) and treatment charts (N=3D22).

<= o:p>

T= he clinical characteristics of cases and controls are presented in Table 1.

T= able 1

C= linical Characteristics of Cases and Controls

<= o:p>

T= he index group thus analyzed had a majority of women (59); mean age for the index gr= oup was 76.5±6.6 years and the depressive episode was a recurrent one (F= 33 code; ICD-10) in 66% of cases. The control group also consisted of 101 pati= ents matched for age (mean 76.6±6.9 years) and sex (42 men and 59 women).= In 72% of control group patients, the depressive episode was recurrent. Age, s= ex, and depression subtype did not differ between groups (t value=3D0.01, df=3D<= /span>201, p=3D0.93, chi2=3D0.0036, df=3D1, p=3D1.0, chi2= =3D0.0928, df=3D1, p=3D0.92, respectively).

<= o:p>

T= he exposure to antidepressant medications was significantly different between groups. While 42% of elderly MDD patients who had attempted suicide prior to hospitalization received antidepressant treatment (index group), 58% of patients in the control group were exposed to antidepressant treatment (a 3= 8% higher rate). This increased rate of exposure was statistically significant, chi2=3D5.4, df=3D1, p=3D0.02. Exposure to antidepressants conferred = a protective effect with an odds ratio, OR=3D1.94, 95% confidence interval, CI=3D1.1-3.4= .

<= o:p>

T= he various antidepressant drugs groups were distributed differently between the index = and control groups. The most common antidepressants in both groups were the SSRIs, followed by the tricyclic= s, and then the SNRIs. However, the rates of prescription differed between groups with the highest exposure to SSRIs in the control group 29% of all patients vs 21% in the index group, 19% t= ricyclics in both groups, SNRIs in 7% of the control grou= p vs 2% of the index group, and RIMA in 3% of the contr= ol group vs 0% of the index group (chi2=3D10.6, df=3D4, p=3D0.031).

<= o:p>

P= atients had been treated with additional psychotropic compounds. The most frequently prescribed group of drugs was benzodiazepines (28% control group vs 14% of the index group), anti= psychotics (14 vs 18%), and mood stabilizers (3 vs 3%). The increased rate of benzodiazepines prescri= ption among the control group subjects was statistically significant, chi2=3D12.7= , df=3D<= /span>5, p=3D0.026. It is important to note that benzodiazepines were coprescribed with an antidepressant in the majority of patients in both the index and control groups (86 and 93%, respectively).

<= o:p>

T= he majority of patients who had attempted suicide did so by drug overdose inge= stion (54%) followed by wrist cutting (16%) or jumping from heights (11%). In an analysis of risk, it was demonstrated that patients with a history of previ= ous suicide attempt were significantly over-represented in the index group; 41 = vs 15% in the control group, p=3D0.003. The risk rati= o for attempted suicide in a patient with a previous attempt was OR=3D3.69 (95% CI=3D1.9-7.2, chi2=3D15.6, df=3D1, p=3D0.0001).

D= ISCUSSION

<= o:p>

T= he present study indicates that elderly patients treated with antidepressants, mainly = SSRIs, are significantly less likely to have attempte= d to commit suicide within the month previous to hospitalization for MDD than a cohort matched for age and sex. Recent discussions by researchers, regulato= rs, and consumers have presented arguments in favor of a s= uicidogenic potential of the SSRIs. This effect is thought = to be more pronounced in children and adolescents. However, reviewing epidemiolog= ical data of Western populations does not support the hypothesis that antidepressants or, more specifically, SSRIs ca= use increased suicidality in elderly patients with depression (Lapierre, 2003). Two important exam= ples are worth mentioning. First, antidepressant prescribing in Northern Ireland has increase= d over five-fold in the decade 1989-1999. In younger adults there was no associati= on between antidepressant prescribing and suicide. For the older group increas= ed antidepressant prescribing was associated with a reduction in suicide rate = over the 10 years of the study (Kelly et al, 2003). Second, Hall et al (2003) ex= amined the association between trends in antidepressant prescribing and suicide ra= tes in Australia for 1991-2000. Again, while overall national rates of suicide did not fall significantly, incidence decreased in older men and women. These authors ha= ve suggested that the increase in antidepressant prescribing may be a proxy ma= rker for improved overall management of depression and, thus, increased prescrib= ing of SSRIs in general practice may have produced a quantifiable benefit (Hall et al, 2003).

<= o:p>

T= o the best of our knowledge, the present study is the first to directly test the association between exposure to antidepressants and suicide attempts among elderly MDD patients in a case-controlled design. Our findings are consiste= nt with data from epidemiological analyses that describe a direct association between increased SSRIs prescribing and decreas= ed suicide rates in the elderly. In the present study 'real-life' effect was analyzed, in contrast to epidemiological studies, in which population trends are explored.

<= o:p>

T= he present study has several methodological and data-related limitations. Compliance, which may affect suicidality, was not accounted= for. The pharmacological data had limitations such as that treatments were not standardized, data were collected retrospectivel= y, and reliable information on doses and treatment duration were unavailable. Previous suicide attempts are a known risk factor for late life suicide. Th= ese were not controlled for in the present study and thus may have added to gro= up differences. A significant weakness of this study is the low rate of depres= sed patients among subjects who had attempted suicide and the difficulty of extracting complete data in half of these cases. This had limited our abili= ty to match the control group for clinical characteristics such as disease severity. In addition, the admission of elderly patients to our tertiary ce= nter not following a suicide attempt may have been due to different depression severity, physical frailty or compliance problems. These inter-group differ= ences need be taken into account and temper the study's conclusions. On the other hand, the study's strengths are the matching of index patients and control patients as to age and gender, the relatively large sample size, and the compulsory reporting of suicide attempts demanded by the health authorities= .

<= o:p>

R= ecently, using variation across countries over time in SSRI sales and suicide Ludwig= and Marcotte (2005) suggested that expanding access= to SSRIs for adults may be a cost-effective way to save = lives. However, they caution that analyzed randomized trials are not fully informa= tive on this question because of small sample sizes and other limitations. The findings of the present study are of similar trend. In conclusion, we sugge= st that for elderly patients suffering from depression, treatment with SSRIs may confer a protective effect from suicidality. Further prospective studies are needed to confirm our findings.

<= o:p>

A= cknowledgements

<= o:p>

T= his study was supported by an unrestricted research grant from H Lundbeck A/S.

R= EFERENCES

<= o:p>

B= ruce ML, Ten Have TR, Reynolds III CF, Katz II, Schulberg HC, Mulsant BH et al (2004). Reducing suicidal ideation and depressive symptoms in depressed older primary care patients: a randomized controlled trial. JAMA 291: 1081-1091. | Arti= cle | PubMed |

<= o:p>

Beautrais AL (2= 002). A case control study of suicide and attempted suicide in older adults. Suicide Life Threat Behav 32: 1-9. | Article | PubMed |

<= o:p>

Charney DS, Reynolds III CF, Lewis L, Lebowitz BD, Sund= erland T, Alexopoulos GS et al (2003). Depression and Bipolar Support Alliance consensus statement on the unmet needs in diagnosis and treatment of mood disorders in late life. Arch Gen Psychiatry 60: 664-672. | Article | PubMed |

<= o:p>

D= onovan S, Kelleher MJ, Lambourn J, Foster R (1999). The occurrence of suicide following the prescription of antidepressant drugs. Arch Suicide Res 5: 181-192. | Article

<= o:p>

F= ischer LC, Wei F, Solberg LI, Rush WA, Heinrich RL (2003).= Treatment of elderly and other adult patients for depression = in primary care. J Am Geriatr Soc 51: 1554-= 1562. | Article | PubMed |

<= o:p>

Freemantle N, House A, Song F, Mason JM, Sheldon TA (1994). Prescr= ibing selective serotonin reuptake inhibitors as strategy for prevention of suici= de. BMJ 309: 249-253. | PubMed |<= /p>

<= o:p>

Gaynes BN, West SL, Ford CA, Frame P, Klein J, Lohr KN (2004). Screening for suicide risk in adults: a summary of the evidence for= the US Preventive Services Task Force. Ann Intern Med 140: 822-835. | PubMed |

<= o:p>

H= all WD, Mant A, Mitchell PB, Rendle VA, Hickie IB, McManus P (2003). Association between antidepressant prescribing and suicide in Australia, 1991-2000: trend analysis. BMJ 326: 1008-1013. | Article | PubMed |

<= o:p>

H= ealy D (2003). Lines of evidence on the risks of suicide with selective serotonin reuptake inhibitors. Psycho= ther Psychosom 72: 71-79. | Article | PubMed |

<= o:p>

H= ealy D, Whitaker C (2003). Antidepressants and suicide: risk-benefit conundrums. J Psychiatry Neurosci 28: 331-337. | PubMed |

<= o:p>

K= elly CB, Ansari T, Rafferty T, Stevenson M (2003). Antidepress= ant prescribing and suicide rate in Northern Ireland. Eur Psychiatry 18: 325-328. | Article | PubMed |

<= o:p>

Lapierre YD (2003). Suicidality with selective serotonin reuptake inhibitors: valid claim? J Psychiatry Neurosc= i 28: 340-347. | PubMed |

<= o:p>

Ludwig J, Marcotte DE (2005). Anti-de= pressants, suicide, and drug regulation. J Policy Anal Manage 24: 249-272. | Article | PubMed |

<= o:p>

O= 'Connell H, Chin AV, Cunningham C, Lawlor BA (2004). Rec= ent developments: suicide in older people. BMJ 16: 895-899. | Article

<= o:p>

Salzman C, Wong E, Wright BC (2002). Drug and ECT treatment of depression in the elderly, 1996-2001: a Literature Review. Biol Psychiatry 52: 265-284. | Article | PubMed |

<= o:p>

SAS/STAT (1990). Users' Guide Version 6, 4th edn, Vols 1, 2. SAS Institute: Cary, NC.

<= o:p>

Teicher MH, = Glod CA, Cole JO (1993). Antidepressant drugs and the emergence of suicidal tendencies= . Drug Saf 8: = 186-212. | PubMed |

Waern M, Rubenowitz E, Wilhelmson K (2003). Predictors of suicide in the old elderly. Gerontology 49: 328-334. | Artic= le | PubMed |