Journal of Affective Disorders 95 (2006) 95–102www.elsevier.com/locate/jad

Research report

Decline in suicidal ideation among patients with MDD is precededby decline in depression and hopelessness

Petteri Sokero a, Mervi Eerola a,b, Heikki Rytsälä a,c, Tarja Melartin a,d, Ulla Leskelä a,c,Paula Lestelä-Mielonen a,c, Erkki Isometsä a,d,⁎

a Department of Mental Health and Alcohol Research, National Public Health Institute, Helsinki, Finlandb Department of Mathematics and Statistics, University of Helsinki, Helsinki, Finland

c Department of Psychiatry, Helsinki University Central Hospital (HUCH), Peijas Hospital, Vantaa, Finlandd Department of Psychiatry, Helsinki University Central Hospital (HUCH), Helsinki, Finland

Received 28 March 2006; received in revised form 21 April 2006; accepted 24 April 2006Available online 15 June 2006

Abstract

Background: Suicidal ideation is likely to represent a phase preceding suicidal acts among most suicidal patients with majordepressive disorder (MDD). Factors predicting reversal of the suicidal process are unknown. Our aim was to test the hypothesis thata decline in suicidal ideation is preceded by a decline in hopelessness among patients with MDD.Method: Of the 269 Vantaa Depression Study patients with DSM-IV MDD, 103 patients scored ≥6 points at baseline on the Scalefor Suicidal Ideation (SSI). Seventy of these patients were followed-up weekly either until they scored zero points on the SSI, or upto 26 weeks.Results: The median duration for a decline of suicidal ideation to zero was 2.2 months after baseline. The level of baseline suicidalideation, depressive symptoms, and the presence of any personality disorder predicted duration of suicidal ideation. A decline inboth depression (BDI) and hopelessness (HS) independently predicted a decline in suicidal ideation.Limitations: Due to study design, we do not know if suicidal ideation relapsed after the first time the patient reached zero score inthe SSI.Conclusions: Among patients with major depressive disorder having suicidal ideation, the decline in suicidal ideation isindependently predicted by preceding declines in the levels of both depressive symptoms as well as hopelessness. The findings areconsistent with possible causal roles of declines in depression and hopelessness in reversing the suicidal process.© 2006 Elsevier B.V. All rights reserved.

Keywords: Depression; Suicidal ideation; Hopelessness

⁎ Corresponding author. Department of Mental Health and AlcoholResearch, National Public Health Institute, Mannerheimintie 166, FIN-00300 Helsinki, Finland.

E-mail address: erkki.isometsa@ktl.fi (E. Isometsä).

0165-0327/$ - see front matter © 2006 Elsevier B.V. All rights reserved.doi:10.1016/j.jad.2006.04.028

1. Introduction

Suicidal ideation is likely to represent a phasepreceding suicidal acts among most patients withmajor depressive disorder (MDD). In a psychologicalautopsy study, more than half of the subjects completingsuicide during major depression had communicatedtheir intent during the final 3 months (Isometsä et al.,

96 P. Sokero et al. / Journal of Affective Disorders 95 (2006) 95–102

1994), and almost all (95%) attempting suicide hadreported suicidal ideation (Sokero et al., 2003). Thus,suicidal ideation appears to precede the decision to acton suicidal impulses among patients with MDD.However, only a minority of those with suicidal ideationactually attempts suicide, and it remains unclear why formost subjects suicidal ideation actually resolves. Theprevalence of suicidal ideation in patients with MDDranges from 47% to 69% (Asnis et al., 1993; Bronischand Wittchen, 1994; Sokero et al., 2003). Risk factorsidentified for suicidal ideation in depression includeseverity of depression (Zisook et al., 1994; Van Gastel etal., 1997; Pages et al., 1997; Alexopoulos et al., 1999),comorbid personality disorders (Van Gastel et al., 1997),comorbid alcohol dependence or abuse (Pages et al.,1997; Cornelius et al., 1995), comorbid anxiety disorder(Schaffer et al., 2000), female gender (Pages et al., 1997;Schaffer et al., 2000), age (Lynch et al., 1999),unemployment (Pages et al., 1997), life events (Monroeet al., 2001), poor social support (Alexopoulos et al.,1999), hopelessness (Van Gastel et al., 1997; Pages etal., 1997; Rudd, 1990), past suicide attempt (Alexopou-los et al., 1999), psychomotor agitation and, perhapsalso depressed mixed state (DMX) as an indicator of apossibly unrecognized bipolar disorder (Akiskal et al.,2005). Two meta-analyses verify that emergent suicidalideation is not more likely on antidepressant thanplacebo after initiation of antidepressants (Beasley et al.,1991; Montgomery et al., 1995), and two recent studieshave documented the actual effectiveness of treatmentsfor depression in reducing suicidal ideation amongelderly patients with depression (Szanto et al., 2003;Bruce et al., 2004). Nevertheless, the factors causing adecline in suicidal ideation, and thus, reversal of thesuicidal process, are still largely unknown. In this study,we investigated prospectively the short-term course ofsuicidal ideation among psychiatric patients with MDD.The temporal relationships between suicidal ideationand depressive symptoms, level of hopelessness, andlevel of anxiety symptoms were examined weekly. First,we investigated the duration of suicidal ideation and itsmain determinants. Second, we hypothesized that adecline in the level of symptoms, specifically inhopelessness, would be the main determinant for adecline in suicidal ideation.

2. Methods

2.1. Setting

The background and methodology of the VantaaDepression Study (VDS) have been described in detail

elsewhere (Melartin et al., 2002, 2004). In brief, theVDS is a collaborative depression research projectbetween the Department of Mental Health and AlcoholResearch of the National Public Health Institute,Helsinki, Finland, and the Department of Psychiatry ofthe Peijas Medical Care District (PMCD), Vantaa,Finland. Vantaa is the fourth largest city in Finland,with a population of 169000 in 1997, and the PMCDprovides free-of-charge psychiatric services to all of itscitizens. The study protocol of the VDS was approvedby the ethics committee of the PMCD in December1996.

2.2. Screening, diagnostic evaluation, and baselinemeasurements

In the first phase, all patients (n=806) at theDepartment of Psychiatry of the PMCD were screenedfor a possible new episode of DSM-IV MDD (APA,1994) between February 1st, 1997 and May 31st, 1998(Melartin et al., 2002). Patients with a positive findingwere fully informed about the study project, and theirparticipation was requested. Of the 703 eligiblepatients, 542 (77%) gave their written informedconsent.

In the second phase, a researcher using the WHOSCAN 2.0 (Wing et al., 1990) interviewed the 542consenting patients, 269 of whom were subsequentlydiagnosed with DSM-IV MDD and included in thestudy. The diagnostic reliability for MDD has beenfound to be excellent (κ=0.86 [95% CI=0.58–1.0])(Melartin et al., 2002). The Structured Clinical Inter-view for DSM-III-R personality disorders (SCID-II)(Spitzer et al., 1989) was used to assess Axis IIdiagnoses. The cohort baseline measurements includedthe 17-item Hamilton Depression Rating Scale (HAM-D) (Hamilton, 1960), the 21-item Beck DepressionInventory (BDI) (Beck et al., 1961), Beck AnxietyInventory (BAI) (Beck et al., 1988), Beck HopelessnessScale (HS) (Beck et al., 1974), Scale for SuicidalIdeation (SSI) (Beck et al., 1979), Social and Occupa-tional Functioning Assessment Scale of DSM-IV(SOFAS) (Goldman et al., 1992), Interview for RecentLife Events (IRLE) (Paykel, 1983), Interview Measureof Social Relationships (IMSR) (Brugha et al., 1987),and Perceived Social Support Scale-Revised (PSSS-R)(Blumenthal et al., 1987).

Current suicidal ideation was first examined usingthe SSI. SSI is a 19-item observer scale designed toquantify the intensity of current conscious suicideideation in various dimensions of self-destructivethoughts or wishes; e.g. the extent of the wish to

97P. Sokero et al. / Journal of Affective Disorders 95 (2006) 95–102

die, the desire to make an actual suicide attempt, anddetails of any plans. Internal deterrents to an activeattempt and subjective feelings of control and/or“courage” regarding a proposed attempt are alsoquantified. Each item consists of three alternativestatements graded in intensity from 0 to 2, with themaximum total score being 38. Here, moderate tosevere suicidal ideation refers to patients scoring ≥6in the SSI, while no ideation refers to a score of zero.Overall, 103 (38%) of the 269 patients, reportedsuicidal ideation according to SSI during the currentepisode. Risk factors for suicidal behaviour, suicidalideation, and suicide attempt have been reportedelsewhere (Sokero et al., 2003).

2.3. Prospective follow-up of depression with a lifechart

Of the 269 subjects with current MDD initiallyincluded in the study, 198 were still alive at the end ofthe study period, had remained unipolar, and could befollowed-up (Melartin et al., 2004), 8 patients (3%) diedduring the 18 moths after baseline, three (1%) of themby suicide (Sokero et al., 2005). At baseline, themajority (154/198, [78%]) had been taking antidepres-sants in normal adult doses. Patients whose diagnosiswas amended to bipolar disorder during the follow-up(13/269, [5%]) were analysed separately. The outcomeof MDD and comorbid disorders was investigated at 6and 18 months by repeated SCAN 2.0 and SCID-IIinterviews, observer- and self-report scales, and medicaland psychiatric records. A detailed life chart wascreated, with time after baseline divided into threeclasses: (a) state of full remission (0/9 criteria symptomsfor major depressive episode), (b) partial remission (1–4/9 symptoms), and (c) major depressive episode (5+/9symptoms). We used two alternative definitions forduration of the index episode: the uninterrupted durationof the episode in the state of major depressive episode –(1) time with full MDE criteria, and time to the firstonset of state of full remission that lasted at least2 consecutive months – (2) time to full remission(Melartin et al., 2004).

2.4. Weekly follow-up of suicidal ideation andcovariates

The VDS is a research and development projectaimed at promoting educational efforts to enhancescientific knowledge and ensure optimal clinicaltreatment of depressive disorders. A comprehensiveevaluation of patients' suicidality was carried out on a

weekly basis until suicidal ideation resolved. Seventyof the 103 patients with current suicidal ideation atbaseline were followed-up weekly; however, due topoor adherence 33 patients could not be followed-up.The SSI, HS, BAI, and BDI scores were measuredweekly. In order to avoid circularity, we omitted thesuicidality items of the BDI. We initially planned thatthe weekly observation could be discontinued upon apatient receiving two consecutive scores of zero in theSSI. However, this goal was perhaps overly optimistic,and thus, we subsequently decided to analyze theweekly observations after the first score of zero in theSSI. All 70 patients were followed-up from baseline toat least two observations, with the maximum follow-uptime being 26 weeks. For 47 patients suicidal ideationresolved, 8 patients dropped out, and 15 patients werefollowed up for the maximum period. The 70 patientswho were successfully followed up, as compared withthose 33 who did not participate in the weekly follow-up, had higher level of psychopathology, more anxietydisorders (46[66%] vs. 13[39%], χ2 =6.349, df=1,p=.018), more cluster B personality disorders (19[27%] vs. 2[6%], χ2 =6.141, df=1, p=.017), includingborderline personality disorder (16[23%] vs. 2[6%],χ2 =4.387, df=1, p=.05), higher level of hopelessness(12.6±4.7 vs. 10.5±4.8, F=4.083, df=1, p=.046).The 8 patients, who dropped out from the weeklyfollow-up, were more often in-patients at the baseline(5[63%] vs. 16[26%], χ2 =4.543, df=1, p=.05), hadhigher level of depression (HAM-D) (25.8±7.4 vs.20.9±6.1, df=1, F=4.414, p=.04) and anxiety (BAI)(33.5±7.2 vs. 23.5±10.2, df=1, F=7.219, p=.009).The overall demographic characteristics are presentedin Table 1.

2.5. Statistical analysis

The decline of suicidal ideation during the follow-up was studied with survival methods by defining theoutcome as the first time when two consecutive zeromeasurements of SSI were found. The overall declineis displayed with the Kaplan–Meier survival curve.Cox's proportional hazard models with time-varyingcovariates were used to study the influence ofreaching threshold levels in hopelessness, depressionor anxiety scores prior to the decline of suicidalideation while adjusting for the initial scores ofsuicidal ideation. For each measure, the appropriatethreshold level was defined separately. The time-varying covariates representing decline in hopeless-ness, depression or anxiety scores, were given thevalue ‘one’ if the corresponding threshold level

Fig. 1. Decline in proportion of cases with suicidal ideation by theKaplan–Meier survival curve.

Table 2Weekly distribution of SSI scores during follow-up

SSI median score

N 25% 50% 75%

Baseline 70 11.0 15.0 20.3Week 1 70 4.0 11.0 18.3Week 2 70 0.0 9.0 17.3Week 3 70 0.0 6.5 16.0Week 4 66 0.0 7.0 16.0Week 5 57 0.0 7.0 14.5

Table 1Characteristics of the suicidal patients participating in weekly follow-up (n=70)

Characteristic n (%)

SexMales 26 (37)Females 44 (63)

Age (years), mean±S.D. 38.9±10.1Marital statusMarried or co-habiting 31 (44)

Treatment settingIn-patients 21 (30)

Psychiatric comorbidityAlcohol dependence/abuse 24 (34)Anxiety disorder (any) 46 (66)Personality disorder (any) 36 (51)

Cluster A 20 (29)Cluster B 19 (27)Cluster C 26 (37)

Comorbid disorder (any) 57 (81)SuicidalitySI in the history 39 (56)SA in the history 23 (33)SA during the index episode 18 (26)

Status variables at baselineHAM-D score, mean±S.D. 21.4±6.4BDI score, mean±S.D. 27.2±6.4BAI score, mean±S.D. 24.7±10.3HS score, mean±S.D. 12.6±4.7PSSS-R score, mean±S.D. 34.5±12.7SOFAS score, mean±S.D. 48.8±10.9SSI score, mean±S.D. 15.6±5.5

BAI=Beck Anxiety Inventory, BDI=Beck Depression Inventory,HAM-D=Hamilton rating scale for Depression, HS=Beck Hopeless-ness Scale, MDD=major depressive disorder, PSSS-R=PerceivedSocial Support Scale-Revised, SA=suicide attempt, SI=suicidalideation, SOFAS=Social and Occupational Functioning AssessmentScale, SSI=Scale for Suicidal Ideation.Item 3 from HAM-D and item 9 from BDI were excluded from theanalyses in order to avoid circularity.

98 P. Sokero et al. / Journal of Affective Disorders 95 (2006) 95–102

(BDI<10, BAI<10, HS<9) was reached for the firsttime, and ‘zero’ before that. Sensitivity of the resultswas investigated by varying the chosen thresholdvalues. The plausibility of the proportional hazardsassumption was checked by plotting the logarithmsof the cumulative baseline hazards against the follow-up time in appropriate comparison groups, as well aswith residual analyses of the models. Since the datawere collected mostly from outpatients, there weresome missing appointments and therefore, missingweekly measurements. The proportions of missingvalues were on average 32% for SSI, 21% for HS,20% for BAI and 30% for BDI. Therefore, a morerobust measure than the weekly scores of thecovariates was needed in the analyses of decline.SPSS software, version 11.0 (SPSS Inc., 1989–2001),

and the software Stata (StataCorp LP) were used forthe estimations.

3. Results

3.1. Course of suicidal ideation

The overall level of psychopathology of thepatients varied from moderate to high. Suicidalideation resolved in 47 (67%) patients and in 15(21%) it persisted for the whole follow-up period.8 patients (11%) dropped out. The decline in theproportion of cases with suicidal ideation is presentedwith the Kaplan–Meier survival curve in Fig. 1 and inTable 2, in this analysis 50% of the populationreached zero in 2.2 months (9.6 weeks). Among thosereaching zero level of the suicidal ideation, the mediantime for this was 1.6 months (6.8 weeks). For thosepatients having both the weekly follow-up (duration ofsuicidal ideation), and the life chart (time with fullMDE criteria and time to full remission) measuresavailable (N=53), the median time for decline to zeroof suicidal ideation was 2.7 months, the median timespent with full MDD criteria was 2.6 months and themedian time to reach full remission was 4.2 months,

Table 3Cox regression model for the duration of suicidal ideation adjusted forbaseline variables

Variable HR 95% CI p

Age, years 0.99 0.95–1.03 .75HS baseline score 1.02 0.93–1.11 .70BAI baseline score 1.04 0.99–1.08 .11BDI baseline score 0.93 0.87–1.00 .04SSI baseline score 0.88 0.81–0.97 .009Personality disorder (any) 0.28 0.11–0.72 .008

HR=Hazard ratio, HS=Beck Hopelessness Scale, BAI=Beck Anx-iety Inventory, BDI=Beck Depression Inventory, SSI=The Scale forSuicide Ideation.

99P. Sokero et al. / Journal of Affective Disorders 95 (2006) 95–102

respectively. Specifically, the difference in the mediantime for decline of suicidal ideation was notstatistically significant between patients with clusterB personality disorders and those without it(1.7 months [7.4 weeks] vs. 1.6 months [6.7 weeks],p=.59, log rank test).

3.2. Baseline factors predicting the duration of suicidalideation

We used the Cox regression model to study theeffect of risk factors predicting the duration of suicidalideation, and used sex, age, HS baseline score, BAIbaseline score, BDI baseline score, SSI baseline score,PSSS-R baseline score, SOFAS baseline score, maritalstatus, presence of alcohol dependency or abuse,presence of any anxiety disorder, presence of suicidalideation or suicide attempts in the history andpresence of any personality disorder as predictorvariables. Of these baseline factors, the level ofsuicidal ideation, depressive symptoms and presenceof any personality disorder each predicted longerduration of suicidal ideation (Table 3). If variable “anypersonality disorder” was replaced with some otherpersonality disorder diagnosis, the significance waslost. We also created an alternative model including

Table 4Cox proportional hazard models for the decline of suicidal ideation adjusted s(BAI), and hopelessness (HS) and jointly for all

Variable Separate models

Depression Anxiety

HR 95% CI p HR 95% CI p

SSI baseline 0.91 0.84–0.97 .008 0.92 0.86–0.99 .0BDI 7.68 3.73–15.85 <.001BAI 4.70 1.99–11.09 <.0HS

SSI=Scale for Suicide Ideation, BDI=Beck Depression Inventory, BAI=Bec

having or not having an antidepressant as a predictorvariable, but this did not significantly influence thefindings.

3.3. Predictors for decline in suicidal ideation

In separate analyses, decline in hopelessness, de-pressive symptoms and anxiety were each significantpredictors for the decline of suicidal ideation. In allanalyses, adjusting for the initial level of suicidalideation showed that the decline depends significantlyon the severity of the symptoms; the higher the initiallevel, the longer the duration. The importance of theinitial level of suicidal ideation was stable in all separateanalyses. When analysing the influence of decline inhopelessness, depressive symptoms and anxiety symp-toms jointly on the decline of suicidal ideation, theapparent separate effect of anxiety turned out to be non-significant (Table 4), whereas declines both in depres-sion and hopelessness had an independent effect on thedecline of suicidal ideation. This may be due to the factthat correlation between subsequent scores in hopeless-ness and anxiety was as high as 0.8 (for other measuresapproximately 0.4). Similar analyses of decline as forSSI were conducted by treating HS, BAI and BDI asoutcomes (analyses not shown here). They revealed thatthe decline of hopelessness was more rapid than that ofanxiety. This is likely to be the reason why it took overthe effect of a later decline in anxiety.

4. Discussion

Suicidal ideation resolved in the majority of thesuicidal MDD patients during the first 2 to 3 months.Our hypothesis was that a decline in hopelessnesswould be the main determinant for the decline ofsuicidal ideation. However, in the joint analyses thedeclines both in depression and hopelessness indepen-dently predicted the following decline in suicidal

eparately for the normalization of depressive symptoms (BDI), anxiety

Joint model

Hopelessness

HR 95% CI p HR 95% CI p

23 0.92 0.86–0.97 .02 0.90 0.84–0.97 .0045.74 2.69–12.25 <.001

01 1.62 0.59–4.48 .345.90 2.24–15.52 <.001 3.51 1.15–10.73 .03

k Anxiety Inventory, HS=Beck Hopelessness Scale, HR=Hazard ratio.

100 P. Sokero et al. / Journal of Affective Disorders 95 (2006) 95–102

ideation. In our view, this finding is consistent with theinterpretation that they both could have a causal role inreversal of the suicidal process. The duration ofsuicidal ideation was longer for patients with higherlevel of psychopathology, such as initially high level ofsuicidal ideation or depressive symptoms at baseline,or some personality disorder.

4.1. Strengths, limitations and generalizability

The present study has some major methodologicalstrengths. To our knowledge, this is the first study tohave employed a specific scale to measure suicidalideation (SSI) prospectively on weekly basis followingup in a sample of adult patients with MDD and the firststudy to investigate factors preceding decline in suicidalideation. The VDS involves a relatively large (N=269)cohort of both out- and inpatients with MDD, fromwhich the group of suicidal patients (N=103) wasscreened out and followed-up. The patients werecarefully diagnosed using structured interviews withexcellent reliability (κ=0.86) for the diagnosis of MDD(Melartin et al., 2002). In addition, information on allcomorbid Axes I and II disorders at baseline and laterinterviews were used. Methodological details arediscussed in earlier reports (Sokero et al., 2003; Melartinet al., 2002, 2004). We used a pre-determined cut-offpoint (SSI≥6) to define moderate to severe currentsuicidal ideation. In retrospect, this may have beensomewhat high (Beck et al., 1999). In addition, althoughthe internal consistency of SSI was high (Cronbach'sα=0.85–0.90), its inter-rater reliability remains un-known. 70 suicidal patients (68%) could be followed-upon weekly basis. These patients had an overall higherlevel of psychopathology than the VDS cohort overall,or those suicidal cases who did not participate in theweekly follow-up. It is unlikely that the findings withthose 33 suicidal patients included would have beenmarkedly different. If anything, we assume that themedian time for duration of suicidal ideation could havebeen shorter. Suicidal depressive patients commonlydiffer more from the non-suicidal in their subjective thanobjective measures on depression. (Malone et al., 1995;Van Praag and Plutchik, 1984; Cornelius et al., 1995;Oquendo et al., 1999). In our sample there appeared tobe a similar trend. Although our findings were highlysignificant, type II error needs to be considered,regarding some predictors of suicidal ideation. Inorder to reduce complexity, we deliberately focused onthe first time the patient reached zero score in the SSI.We do not know if suicidal ideation relapsed after that. Itis to be noted, that our findings are also dependent on the

chosen threshold levels for depressive and anxietysymptoms and hopelessness. However, the findings arerobust and according to the sensitivity analysesconducted, would not be markedly different with otherthreshold levels. Finally, because the study wasconducted in a secondary level psychiatric setting, itwas inevitable that there were some missed appoint-ments. It is impossible to exclude the possibility thatduring some of these missed appointments, level of SSIcould have already reached zero but then relapsed later.This could have led us to somewhat overestimate theuninterrupted duration of suicidal ideation, but isunlikely to cause other biases.

4.2. Decline of suicidal ideation

The duration of decline in suicidal ideation isstrongly associated with the initial level of symptoms;the higher the initial level, the longer the duration.Personality disorders overall had also a significantimpact on the duration of suicidal ideation. Contrary toour expectations, this was more related to overall, ratherthan specifically to cluster B or borderline personalitydisorder. Suicidal ideation appears to resolve graduallyafter depressive symptoms and hopelessness havestarted to alleviate. The duration of ideation approxi-mately corresponds the time the patients fulfil thecriteria for a major depressive episode. Thus, even somedecrease in the level of depression seems to be enoughto initiate the decline in the intensity of suicidal ideation.This is consistent with earlier findings (Szanto et al.,2003; Bruce et al., 2004) among elderly depressivesabout the impact of treatment interventions to suicidalideation. There has been an ongoing debate onantidepressants and suicidal behaviour (Healy, 2003;Casey, 2004; Painuly and Basu, 2004); most of thepatients in our sample were on antidepressants, andhaving or not having them had no significant influenceon the duration of suicidal ideation.

To our knowledge, this is the first study investigatingfactors explaining the reversal of suicidal ideation. Wefound that the decline of suicidal ideation is stronglyassociated with the preceding decline of depressivesymptoms, level of hopelessness and anxiety. Hope-lessness, severity of depression and anxiety are allidentified risk factors for suicidal behaviour. Wehypothesized that a decline in the level of hopelessnesswould be the main determinant for a decline in suicidalideation. Hopelessness as it occurs in depressed patientsmay be viewed as having both state and traitcharacteristics. During depression, hopelessness esca-lates and then subsides along the course of illness (Beck

101P. Sokero et al. / Journal of Affective Disorders 95 (2006) 95–102

et al., 1990). Cognitive research on suicide and riskprediction has developed a model of suicidal behaviourin which hopelessness is a key psychological variable(Beck and Weishaar, 1990). In our joint analysis, thedecline of depression and hopelessness were thesignificant independent risk factors. We examinedwhich of these three factors appear to have a plausiblecausal relationship to decline in suicidal ideation. Thecriteria for causality, as reviewed by Rothman andGreenland (1998) are strength of association, consis-tency, specificity, temporality (the most important one),biologic gradient, plausibility, coherence, experimentalevidence and analogy. Both depressive symptoms andhopelessness have a strong and consistent associationwith suicidal ideation (Sokero et al., 2003; Van Gastel etal., 1997; Pages et al., 1997; Malone et al., 2000), andthey are plausible and theoretically coherent risk factorsfor suicidal behaviour. Experimental evidence from thetwo reports (Szanto et al., 2003; Bruce et al., 2004) oneffectiveness of treatments for depression to alleviatealso suicidal ideation at least among elderly depressivesexists, although these studies cannot inform whether thisalleviation is related to depressive symptoms per se, orthe role of underlying hopelessness. To our knowledge,our findings provide first information on the temporalcourse, which is crucial when estimating potentialcausal role.

Overall, our findings are consistent with the interpre-tation that declines in both depression and hopelessnesscould have a causal role in reversing the suicidal process.However, we can never exclude the possibility ofexistence of other possible, perhaps even more primarycausal factors we were not able to measure. Futurestudies may confirm and further clarify (or falsify) ourworking hypothesis by prospectively following suicidalideation plus both depressive symptoms as well ashopelessness, and investigating the effectiveness oftreatments for depression, or perhaps psychotherapiesspecifically targeted at hopelessness, in reversingsuicidal ideation among adult patients with MDD.

References

Akiskal, H.S., Benazzi, F., Perugi, G., Rihmer, Z., 2005. Agitated“unipolar” depression re-conceptualized as a depressive mixedstate: implications fort he antidepressant-suicide controversy. JAD85, 245–258.

Alexopoulos, G.S., Bruce,M.L., Hull, J., Sirey, J.A., Kakuma, T., 1999.Clinical determinants of suicidal ideation and behavior in geriatricdepression. Archives of General Psychiatry 56, 1048–1053.

American Psychiatric Association, 1994. Diagnostic and StatisticalManual of Mental Disorders, 4th edn. APA, Washington, DC.DSM-IV.

Asnis, G.M., Friedman, T.A., Sanderson, W.C., Kaplan, M.L., vanPraag, H., Harkavy-Freidman, J.M., 1993. Suicidal behaviors inadult psychiatric outpatients: I. Description and prevalence.American Journal of Psychiatry 150, 108–112.

Beasley, C.M., Dornseif, B.E., Bosomworth, J.C., Sayler, M.E.,Rampey Jr., A.H., Heiligenstein, J.H., Thompson, V.L., Murphy,D.J., Masica, D.N., 1991. Fluoxetine and suicide: a meta-analysis of controlled trials of treatment for depression. BMJ303, 685–692.

Beck, A.T., Weishaar, M.E., 1990. Suicide risk assessment andprediction. Crises 22, 22–30.

Beck, A.T., Ward, C.H., Mendelson, M., Moch, J.E., Erbauch, J.K.,1961. An inventory for measuring depression. Archives of GeneralPsychiatry 4, 561–571.

Beck, A.T., Weismann, A., Lester, D., Trexler, L., 1974. The measureof pessimism: the hopelessness scale. Journal of Consulting andClinical Psychology 42, 861–865.

Beck, A.T., Kovacs, M., Weissman, A., 1979. Assessment of suicidalintention: a scale for suicidal ideation. Journal of Consulting andClinical Psychology 47, 343–352.

Beck, A.T., Brown, G., Epstein, N., Steer, R.A., 1988. Aninventory for measuring clinical anxiety: psychometric proper-ties. Journal of Consulting and Clinical Psychology 56,893–897.

Beck, A.T., Brown, G., Berchick, R.J., Stewart, B.L., Steer, R.A.,1990. Relationship between hopelessness and ultimate suicide: areplication with psychiatric outpatients. American Journal ofPsychiatry 147, 190–195.

Beck, A.T., Brown, G.K., Steer, R.A., Dahlsgaard, K.K., Grisham,J.K., 1999. Suicide ideation at its worst point: a predictor of even-tual suicide in psychiatric outpatients. Suicide & Life-ThreateningBehavior 29, 1–9.

Blumenthal, J.A., Burg, M.M., Barefoot, J., Williams, R.B., Haney, T.,Zimet, G., 1987. Social support, type A behaviour, and coronaryartery disease. Psychosomatic Medicine 49, 331–340.

Bronisch, T., Wittchen, H.-U., 1994. Suicidal ideation and suicideattempts: comorbidity with depression, anxiety disorders, andsubstance abuse disorder. European Archives of Psychiatry andClinical Neuroscience 244, 93–98.

Bruce, M.L., Ten Have, T.R., Reynolds, C.H., Katz, I.I., Schulberg, H.C., Mulsant, B.H., Brown, G.K., McAvay, G.J., Pearson, J.L.,Alexopoulos, G.S., 2004. Reducing suicidal ideation and depres-sive symptoms in depressed older primary care patients. Arandomized controlled trial. Journal of the American MedicalAssociation 291, 1081–1091.

Brugha, T.S., Sturt, E., MacCarthy, B., Potter, J., Wykes, T.,Bebbington, P.E., 1987. The interview measure of social relation-ships: the description and evaluation of a survey instrument forassessing personal social resources. Social Psychiatry 22,123–128.

Casey, P., 2004. SSRI and suicide. Psychotherapy and Psychosomatics73 (4), 259–260.

Cornelius, J.R., Salloum, I.M., Mezzich, J., Cornelius, M.D., Fabrega,H., Ehler, J.G., Ulrich, R.F., Thase, M.S., Mann, J.J., 1995.Disproportionate suicidality in patients with comorbid majordepression and alcoholism. American Journal of Psychiatry 152,358–364.

Goldman, H.H., Skodol, A.E., Lave, T.R., 1992. Revising Axis V forDSM-IV: a review of measures of social functioning. AmericanJournal of Psychiatry 149, 1148–1156.

Hamilton, M., 1960. A rating scale for depression. Journal ofNeurology, Neurosurgery and Psychiatry 23, 56–62.

102 P. Sokero et al. / Journal of Affective Disorders 95 (2006) 95–102

Healy, D., 2003. Lines of evidence on the risks of suicide withselective serotonin reuptake inhibitors. Psychotherapy and Psy-chosomatics 72 (2), 71–79.

Isometsä, E.T., Henriksson, M.M., Aro, H.M., Heikkinen, M.E.,Kuoppasalmi, K.I., Lönnqvist, J.K., 1994. Suicide in majordepression. American Journal of Psychiatry 151, 530–536.

Lynch, T.R., Johnson, C.S., Mendelson, T., Robins, C.J., Krishnan, K.R.K., Blazer, D.G., 1999. New onset and remission of suicidalideation among a depressed adult sample. Journal of AffectiveDisorders 56, 49–54.

Malone, K.M., Haas, G.L., Sweeney, J.A., Mann, J.J., 1995. Majordepression and the risk of attempted suicide. Journal of AffectiveDisorders 34, 174–185.

Malone, K.M., Oquendo, M.A., Haas, G.L., Ellis, S.P., Li, S., Mann,J.J., 2000. Protective factors against suicidal acts in majordepression: reasons for living. American Journal of Psychiatry157, 1084–1088.

Melartin, T.K., Rytsälä, H.J., Leskelä, U.S., Lestelä-Mielonen, P.S.,Sokero, T.P., Isometsä, E.T., 2002. Current comorbidity of DSMIV major depressive disorder in psychiatric care – VantaaDepression Study. Journal of Clinical Psychiatry 63, 126–135.

Melartin, T.K., Rytsälä, H.J., Leskelä, U.S., Lestelä-Mielonen, P.S.,Sokero, T.P., Isometsä, E.T., 2004. Severity and comorbiditypredict episode duration and recurrence of DSM-IV majordepressive disorder. Journal of Clinical Psychiatry 65, 810–819.

Monroe, S.C., Harkness, K., Simons, A.D., Thase, M.E., 2001. Lifestress and the symptoms of major depression. Journal of Nervousand Mental Diseases 180, 168–175.

Montgomery, S.A., Dunner, D.L., Dunbar, G.C., 1995. Reduction ofsuicidal thoughts with paroxetine in comparison with referenceantidepressants and placebo. European Neuropsychopharmacol-ogy 5, 5–13.

Oquendo, M.A., Malone, K.M., Ellis, S.P., Sackheim, H.A., Mann,J.J., 1999. Inadequacy of antidepressant treatment for patientswith major depression who are at risk for suicidal behavior.American Journal of Psychiatry 156, 190–194.

Pages, K.P., Russo, J.E., Roy-Byrne, P.P., Ries, R.K., Cowley, D.S.,1997. Determinants of suicidal ideation: the role of substance usedisorders. Journal of Clinical Psychiatry 58, 510–515.

Painuly, N., Basu, D., 2004. SSRI and suicide? Psychotherapy andPsychosomatics 73 (4), 261–262.

Paykel, E.S., 1983. Methodological aspects of life event research.Journal of Psychosomatic Research 27, 341–352.

Rothman, K.J., Greenland, S., 1998. Causation and causal inference.In: Rothman, K.J., Greenland, S. (Eds.), Modern Epidemiology.Lippincott-Raven Publishers, Philadelphia, pp. 7–28.

Rudd, M.D., 1990. An integrative model of suicidal ideation. Suicide& Life-Threatening Behavior 20 (1), 16–30.

Schaffer, A., Levitt, A.J., Bagby, R.M., Kennedy, S.H., Levitan, R.D.,Joffe, R.T., 2000. Suicidal ideation in major depression: sexdifferences and impact of comorbid anxiety. Canadian Journal ofPsychiatry 45, 822–826.

Sokero, T.P., Melartin, T.K., Rytsälä, H.J., Leskelä, U.S., Lestelä-Mielonen, P.S., Isometsä, E.T., 2003. Suicidal ideation andattempts among psychiatric patients with major depressivedisorder. Journal of Clinical Psychiatry 64, 1094–1100.

Sokero, T.P., Melartin, T.K., Rytsälä, H.J., Leskelä, U.S., Lestelä-Mielonen, P.S., Isometsä, E.T., 2005. Prospective study of riskfactors for attempted suicide among patients with DSM-IV majordepressive disorder. British Journal of Psychiatry 186, 314–318.

Spitzer, R., Williams, J.B.W., Gibbon, M., First, M.B., 1989.Structured Clinical Interview for DSM-III-R Personality Disorder(SCID-II). Biometrics Research Department, New York StatePsychiatric Institute, New York.

SPSS Inc., 1989–2001. Release 11.0.1. Statistical Package for theSocial Sciences for Windows. Chicago, IL, USA.

StataCorp LP. Release 9. Statistical Software for Professionals.College Station, Texas, USA.

Szanto, K., Mulsant, B.H., Houck, P., Dew, M.A., Reynolds, C.H.,2003. Occurrence and course of suicidality during sort-termtreatment of late-life depression. Archives of General Psychiatry60, 610–617.

Van Gastel, A., Schotte, C., Maes, M., 1997. The prediction of suicidalintent on depressed patients. Acta Psychiatrica Scandinavica 96,254–259.

Van Praag, H.M., Plutchik, R., 1984. Depression type and depressionseverity in relation to risk of violent suicide attempt. PsychiatryResearch 12, 333–338.

Wing, J.K., Babor, T., Brugha, T., Burke, J., Cooper, J.E., Giel, R.,Jablenski, A., Reiger, D., Sartorius, N., 1990. SCAN. Schedulesfor clinical assessment in neuropsychiatry. Archives of GeneralPsychiatry 47, 589–593.

Zisook, S., Arleen, G., Sledge, P., Schuchter, S.R., 1994. Reportedsuicidal behavior and current suicidal ideation in a psychiatricoutpatient clinic. Annals of Clinical Psychiatry 6 (1), 27–31.