Articol original 1.qxd

ARTICOLE ORIGINALE
COMORBID ANXIETY DELAYS TREATMENT
RESPONSE AND INCREASES RELAPSE RISK IN
LATE-LIFE DEPRESSION: A CONTROLLED STUDY
Carmen Andreescu, M.D. *, Eric J. Lenze, M.D. *, Mary Amanda Dew, Ph.D. *, Amy E. Begley, M.A. *, Benoit
H. Mulsant, M.D. **, Alexandre Y. Dombrovski, M.D. *, Bruce G. Pollock, M.D., Ph.D. ***, Jacqueline Stack,
M.S.N. *, Mark D. Miller, M.D. *, Charles F. Reynolds III, M.D. *
Rezumat:
Summary:
SCOP. Studiul a cercetat dacã simptomele anxie- AIMS: This study examines whether co-morbid tãþii comorbide au valoare predictivã a rãspunsului anxiety symptoms predict acute treatment response terapeutic ºi a recurenþei depresiei majore în cursul a and recurrence of major depression during two years doi ani de tratament de întreþinere în cazul depresiei of maintenance treatment in late- life depression METODÃ. Datele au fost obþinute dintr-un studiu METHOD: Data were drawn from a randomized, dublu-orb, randomizat, de farmacoterapie ºi psihoterapie double-blind study of pharmacotherapy and interper- interpersonalã pe pacienþi de cel puþin 70 de ani cu LLD. sonal psychotherapy for patients age 70 and over with Severitatea anxietãþii anterioare tratamentului a fost LLD. Pretreatment severity of anxiety was measured mãsuratã cu Inventarul Scurt al Simptomelor. Analiza using the Brief Symptom Inventory. Survival analysis statisticã (survival analysis) a testat relaþia temporalã tested the effect of pretreatment anxiety on response dintre anxietatea anterioarã tratamentului ºi apariþia rãspunsului terapeutic ºi al recurenþei depresiei. RESULTS: Patients with greater pretreatment REZULTATE. Pacienþii cu anxietate anterioarã tra- anxiety took on average 4.3 weeks longer to respond to tamentului mai mare au rãspuns, în medie, cu 4,3 sãp- depression treatment and had higher rates of recur- tamâni mai târziu la tratamentul antidepresiv în timpul rence of depression during maintenance treatment. tratamentului de menþinere. Ratele recurenþei au fost Actuarial recurrence rates were 29% (pharmacother- de 29% (farmacoterapie, anxietate redusã), 58% (far- apy, lower anxiety), 58% (pharmacotherapy, higher macoterapie, anxietate mai mare), 54% (placebo, an- anxiety), 54% (placebo, lower anxiety) and 81% xietate redusã) ºi 81% (placebo, anxietate mai mare). CONCLUZIE. Identificarea mai atentã ºi mana- CONCLUSION: Improved identification and gementul anxietãþii în LLD sunt necesare pentru management of anxiety in LLD are needed to achieve obþinerea rãspunsului terapeutic ºi stabilitatea sa. Cuvinte cheie: anxietate, depresie majorã, vârsta INTRODUCTION
in LLD. Thus, several studies have found that greater Co-morbid anxiety is common in depressive disor- severity of anxiety symptoms is associated with an ders, both in middle and later life. In community sam- increased risk of treatment dropout (9, 10), a decreased ples of younger depressed adults, the point prevalence response to acute antidepressant treatment (9-11), or a longer of co-morbid anxiety disorders ranges from 33% (1) to time to both response (6, 12, 13) and remission (14, 15). 51% (2); with a 46% point-prevalence in a clinical sam- Although the impact of anxiety on response and ple (3). In community samples of older adults with late- recurrence of major depression has been previously life depression (LLD), the point prevalence of co-mor- studied extensively in general adult populations, its rel- bid anxiety disorders ranges from 26% (4) to 48% (5).
evance to long term treatment response in late life In clinical samples of older patients with LLD, co-mor- depression has received much less attention (16, 17) bid anxiety disorders are diagnosed in 3% to 65% (6-8). and has not been examined in a controlled maintenance Beyond the high rates of coexistence, co-morbid trial. Maintenance outcomes in LLD and the factors anxiety has been often cited as a clinically relevant which moderate those outcomes are critical, given the problem due to its impact on acute treatment response brittle nature of response in this age group (18, 19). To * The Advanced Center for Interventions and Services Research for Late-life Mood Disorders and the John A. Hartford Center of Excellence inGeriatric Psychiatry, Department of Psychiatry, University of Pittsburgh School of Medicine; ** Center for Addiction and Mental Health, University of Toronto, Canada; *** The Rotman Research Institute, Baycrest Center for Geriatric Care, University of Toronto, Canada Translated, with permission, from the British Journal of Psychiatry (vol.190, pp. 344-349), Royal College of Carmen Andreescu ºi colab.: Comorbid anxiety delays treatment response and increases relapse risk our knowledge, the only published data addressing pharmacotherapy received paroxetine (with adjunctive these long-term outcomes were obtained during a 2- medication if required) for the remainder of their study year naturalistic follow-up. In this uncontrolled study participation. Patients randomized to placebo had pretreatment anxiety symptoms were not related to time paroxetine (and adjunctive medication) slowly tapered to recurrence during two years of open pharmacothera- over 6 weeks under double-blind conditions. All patients were allowed to remain on a stable dose of Thus, given the high recurrence rate of LLD (21) lorazepam if it had been required during the acute or and the increased morbidity and mortality risks associ- continuation treatment phases. Patients remained in ated with LLD (22-24) as well as the lack of controlled maintenance therapy for two years or until recurrence data regarding impact of pretreatment anxiety on long of a major depressive episode. Recurrence required a term treatment of LLD, further examination of anxiety HDRS score of >15, meeting DSM-IV criteria for a as a predictor not only of response but of recurrence major depressive episode during a SCID interview, and would greatly benefit clinicians in planning treatment.
having an independent geriatric psychiatrist confirm Accordingly, we conducted an analysis to assess the diagnosis. Assessors were blind to treatment whether pretreatment co-morbid anxiety predicts treat- assignment. All patients provided written informed ment outcomes during both acute and maintenance consent. For this data analysis, we collapsed the IPT treatment of major depression in old age. We hypothe- and non-IPT groups because IPT was not shown to pre- sized that greater pretreatment severity of anxiety vent recurrence in the primary outcome analysis, while symptoms would predict poor treatment outcome, including both a longer time to response during acute Symptoms of anxiety were measured using the treatment and an increased rate of and shorter time to self-report anxiety scale from the Brief Symptom recurrence during maintenance treatment.
Inventory [BSI, (29)]. The BSI is a validated self-report scale developed from the SCL-90-R with strongtest–retest and internal consistency reliabilities. Factor analytic studies of the internal structure of the scale Data for this analysis were provided by the second have demonstrated its construct validity (29). The anx- study of Maintenance Therapies in Late Life iety subscale consists of six items: “nervousness or Depression (MTLD-II) conducted at the University of shakiness inside”, “suddenly scared for no reason”, Pittsburgh Intervention Research Center for the Study “feeling fearful”, “feeling tense or keyed up”, “spells of of Late-Life Mood Disorders between 1999 and 2004.
terror or panic”, and “feeling so restless you couldn’t sit Details of the study protocol are described elsewhere still”. Each item is rated on a 5-point scale (0 = symp- (19). In brief, participants were 70 and older, with a tom not present, 4 = extremely severe). We used both a diagnosis per Structured Clinical Interview for DSM- categorical and a continuous form of the BSI anxiety IV (SCID) (25) of non-psychotic, non-bipolar major measure. We analyzed BSI scores (Cronbach’s alpha depressive disorder (single-episode or recurrent), a 17- for the present sample = .84) on a continuum and also item Hamilton Depression Rating Scale (HDRS) of 15 we also dichotomized those with higher versus lower or higher (26), and a Mini Mental State Examination anxiety by using a median split (median value for the sample = 1.0). We present in this paper the results In the acute phase, patients received open pharma- based on the categorical approach because it has more cotherapy and weekly interpersonal psychotherapy relevance to the categorical decisions clinicians are (IPT) (28) until they achieved response (defined as a HDRS score of 10 or less for three consecutive weeks).
The analyses included 181 subjects who partici- Pharmacotherapy consisted of paroxetine started at 10 pated in the acute treatment phase. Of these, 116 main- mg/day and titrated as necessary up to a maximum of tained response during continuation treatment and were 40 mg/day. Adjunctive pharmacotherapy with bupro- randomly assigned to maintenance treatment. Pre-treat- pion, nortriptyline, or lithium was used when required ment BSI scores were available on 170 subjects enter- to achieve response (N = 69). Adjunctive lorazepam ing the acute phase. Of these, 109 participated in ran- (0.5 – 2 mg/day) was also used in 65 patients. Patients who responded to acute treatment entered 16-weeks of continuation treatment to stabilize their Statistical analysis
response; they received the same pharmacotherapy and We used Kaplan-Meier survival analysis to assess IPT every two weeks. Patients who maintained the effect of pre-treatment anxiety symptoms (BSI response during continuation treatment were then ran- scores) on time to response. In order to analyze the domly assigned to one of four maintenance treatments: influence of lorazepam on time to response (30), we 1) pharmacotherapy/monthly clinical management vis- compared the time to response in the group receiving its; 2) placebo/monthly clinical management visits; 3) lorazepam versus the group not receiving lorazepam.
pharmacotherapy/monthly maintenance IPT; 4) place- Further, we stratified the sample based on presence or bo/monthly maintenance IPT. Patients randomized to absence of lorazepam use. In order to control for other Revista Românã de Psihiatrie, seria a III-a, vol. IX, nr. 4, 2007 potential confounders, we subsequently fit Cox propor- response and began maintenance treatment, while of tional hazards models for each outcome, stratifying on those with lower BSI 75% (66/88) achieved response severity of depression to estimate the unique effects of and began maintenance treatment (chi-square =6.09, df anxiety on acute treatment outcomes. We controlled for baseline depression severity as measured by the Patients with higher BSI had a median time to HDRS scores, with the four anxiety–related items response significantly longer than those with lower –items 9, 10, 11 and 15— removed (12, 31, 32). BSI: 11.0 [95%CI: 7.7-13.9] vs. 6.7 [5.9-7.9] weeks To assess the effect of co-morbid symptomatic (Wilcoxon chi square= 6.26, df =1, p=0.01).
anxiety on time to recurrence during maintenance treat-ment, we stratified the sample based on randomization Effects of adjunctive lorazepam
to paroxetine or placebo and performed Kaplan-Meier Patients who received adjunctive lorazepam analyses in four groups: 1) pharmacotherapy with lowerBSI scores (N= 35); 2) pharmacotherapy with higher (N=65) had a median time to response significantly BSI scores (N=23); 3) placebo with lower BSI scores longer than those who did not (N=120): 12.4 [95%CI: (N=31); 4) placebo with higher BSI scores (N= 20).
8.4-14.7] vs. 6.9 [5.6-7.9] weeks (Wilcoxon = 16.81, df=1, p<0.0001). The mean (SD) dose of lorazepamreceived by patients with higher or lower BSI scores did not differ significantly: 1.03 (0.60) vs. 0.92 (0.44) Participants’ baseline demographic and clinical mg/day (t=-0.75, df =61, p=0.45). However, as would characteristics are presented in Table 1. be expected, lorazepam use was correlated with higher Effect of Symptomatic Co-morbid Anxiety on
BSI scores (phi=0.31). Therefore, we analyzed post Response during Acute Treatment
hoc the time to response separately in patients who At baseline, 82 patients had higher BSI scores received and did not receive lorazepam, contrasting (above median split) and 88 had lower BSI scores.
those with higher BSI and lower BSI. Among patient Among patients with higher BSI, 52% (43/82) achieved who received lorazepam, those with higher BSI had a Table 1: Demographic and clinical characteristics of patients by level of Brief Symptom Inventory anxiety scores. Variable
Lower BSI
Higher BSI
(Q9, Q10, Q11, Q15) Age at onset of first episode of depression % patients with first episode lorazepam during acute phase (N) Lorazepam dose (mg/day) of any anxiety disorder at baseline (N) Paroxetine Dose (at the end All results are mean (SD) unless indicated otherwise*CIRS-G = Cumulative Illness Rating Scale for Geriatrics; **HDRS 17 = 17-item version of the Hamilton Depression Rating Scale;***Natural Log used in the analyses. Means and standard deviations reported in their original units.
Carmen Andreescu ºi colab.: Comorbid anxiety delays treatment response and increases relapse risk Figure 1: Anxiety symptoms and time toresponse. Patients with higher severity ofsymptoms at baseline averaged 4.3 weekslonger response time. (Wilcoxon chi-square=6.26, df =1, p=0.012) median time to response significantly longer than those Effect of Symptomatic Co-morbid Anxiety on
with lower BSI: 13.9 [95%CI: 11.0-17.1] vs. 7.9 Recurrence during Maintenance Treatment
[95%CI: 5.9-13.6] weeks (Wilcoxon chi-square=4.48, A higher BSI predicted an increased rate of recur- df=1, p=0.03). Among patients who did not receive rence (Wald chi-square=7.05, df =1, p=0.008, 95% CI lorazepam, the difference in time to response between patients with higher versus lower BSI was not signifi- Time to recurrence from randomization (see cant (Wilcoxon chi-square=0.0858, df=1, p= 0.77).
Figure 2) differed across the four groups, with the high- The mean (SD) final dose of paroxetine received er BSI group having a shorter time to recurrence (Log- by patients with higher or lower BSI did not differ: 26.3 Rank= 15.00, df=3, p=0.002). Recurrence rates (10.9) vs. 24.2 (10.4) mg/day (t=-1.27, df =168, (adjusting for censoring) were 29% (pharmacotherapy with lower BSI scores), 58% (pharmacotherapy with The effect of symptomatic anxiety on time to higher BSI scores), 54% (placebo with lower BSI response remained significant in our Cox model, strati- scores) and 81% (placebo with higher BSI scores). fying on baseline HDRS score (minus anxiety items), Among patients receiving pharmacotherapy, time (Hazard ratio= 0.65, 95% CI: 0.45-0.93, p=0.02).
to recurrence was significantly shorter for those with Figure 2: Co-morbid Anxiety symptoms and time to recurrence. Actuarial recurrence rates were 29% (drug in low BSI), 58% (drug in high BSI), 54% (placebo in low BSI, and 81% (placebo in high BSI). (Chi- Revista Românã de Psihiatrie, seria a III-a, vol. IX, nr. 4, 2007 Table 2: Number of Subjects with higher versus lower BSI in each outcome group higher BSI scores than for those with lower BSI scores response. The use of lorazepam per se probably did not (Log-Rank= 5.66, df= 1, p=0.02). Among patients on prolong time to response, because patients receiving placebo, time to recurrence did not differ significantly adjunctive lorazepam but having lower BSI scores had between those with higher or lower BSI scores (Log- similar time to response as patients not receiving Rank = 2.54, df =1, p=0.11). Among patients with adjunctive lorazepam. This observation is consistent higher BSI scores, time to recurrence did not differ with our previous study (30) that reported that adjunc- between those on placebo or paroxetine (Log- tive lorazepam did not slow the antidepressant response Rank=1.95, df =1, p=0.16). Among patients with lower in elderly depressed patients. However, patients with BSI scores, time to recurrence was significantly shorter higher BSI not receiving adjunctive lorazepam had for those on placebo than on paroxetine (Log- shorter time to response than those with higher BSI who received lorazepam. One possible explanation - Because these findings suggested a moderator that deserves further exploration - is that patients with effect of anxiety, a separate Cox Regression examined higher BSI who needed adjunctive lorazepam differ the possible moderator effect of anxiety (measured by clinically from patients with higher BSI who did not BSI) on maintenance treatment outcomes, by analyzing need adjunctive lorazepam. This difference might be the interaction between BSI scores and pharmacothera- related to a higher preponderance of GAD-like symp- py. The results did not confirm a moderator effect (chi- toms in the group who needed adjunctive lorazepam, as square=0.49, df =1, p=0.48). The power to detect a GAD more often than other anxiety disorders is associ- moderator effect was low (0.22) and Hazard Ratio for the interaction was 1.5 (CI = 0.48-4.68). Our study was limited in its power to detect a We repeated the analysis for both acute and main- moderator effect, that is, interactions between treatment tenance phases using the BSI as a continuous measure and co-existing anxiety. We were able to detect main and the results were similar (data not shown but avail- effects of pharmacotherapy and of anxiety on recur- rence, but lacked sufficient power to detect interactionbetween pharmacotherapy and anxiety.
DISCUSSION
This study is the first randomized controlled trial that demonstrates the limited efficacy of standard phar- Our study is the first to show that high pretreat- macotherapy in LLD with coexisting anxiety to get and ment anxiety symptoms increase not only the risk of keep patients well. It is important to emphasize that non-response in acute treatment but also the risk of patients treated in this study received very intensive recurrence in the first two years after response to treat- management, with clinicians and psychiatrists review- ment in late life depression. In other words, elderlypatients who start treatment with higher severity of anx- ing cases weekly and refining treatment plans to mini- iety have both a poorer acute response and a more brit- mize attrition and maximize response. Also, adjunctive tle long-term response to pharmacotherapy. These pharmacotherapy strategies, which were instrumental results demonstrate a strong negative impact of anxiety in many patients achieving response and which were symptoms on short- and long-term outcome of depres- continued during the maintenance phase, were still not sion in old age, even with optimal treatment. These enough to protect most patients with co-morbid anxiety findings for acute treatment effects confirm previous from recurring. Even under these intensive treatment reports (6, 10, 12) that greater pretreatment anxiety is conditions that go beyond regular clinical care, co-mor- associated with poorer response during acute treatment of bid anxiety had a prominent negative effect on acute LLD. We also found that these co-morbid anxiety symp- toms increase the risk of recurrence. To our knowledge, Overall, our findings suggest limited efficacy of only one previous uncontrolled follow-up study has current medications with regard to mitigating the examined the impact of co-morbid anxiety on long-term impact of co-morbid anxiety on response and recur- outcome of LLD. In this naturalistic study, pretreatment rence, even though selective serotonin reuptake anxiety did not predict time to recurrence (20).
inhibitors (such as paroxetine, used in this study) are We found that patients with higher BSI scores and indicated for the treatment of both anxiety and depres- adjunctive lorazepam treatment had increased time to sion. It is also worth noting that adding lorazepam to Carmen Andreescu ºi colab.: Comorbid anxiety delays treatment response and increases relapse risk paroxetine in patients with higher anxiety did not 11. Steffens DC, McQuoid DR: Impact of symptoms of gener- improve outcomes. Alternative treatment options alized anxiety disorder on the course of late-life depression. Am JGeriatr Psychiatry 2005; 13(1):40-7 should be considered for these patients.
12. Dew MA, Reynolds CF, 3rd, Houck PR, Hall M, Buysse Given the detrimental effect of anxiety on long- DJ, Frank E, Kupfer DJ: Temporal profiles of the course of depres- term course of depression and the limited benefit sion during treatment. Predictors of pathways toward recovery in the demonstrated here even with optimal treatment, clini- elderly.[see comment]. Archives of General Psychiatry 1997; cians are left with the challenge of what they can do to 13. Lenze EJ, Mulsant BH, Dew MA, Shear MK, Houck P, improve outcome in this group of patients (33). Expert Pollock BG, Reynolds CF, 3rd: Good treatment outcomes in late-life consensus guidelines (34) recommend maximizing the depression with comorbid anxiety. J Affect Disord 2003; 77(3):247- antidepressant. It is possible that doses of paroxetine higher than those used in this study would have yielded 14. Alexopoulos GS, Katz IR, Bruce ML, Heo M, Ten Have T, Raue P, Bogner HR, Schulberg HC, Mulsant BH, Reynolds CF, better outcomes in anxious patients (35). However, older 3rd, Group P: Remission in depressed geriatric primary care patients: adults may not tolerate very high doses of antidepres- a report from the PROSPECT study. American Journal of Psychiatry sants, given the frequent medical comorbidy and sensi- tivity to medications’ side effects in this population.
15. Clayton PJ, Grove WM, Coryell W, Keller M, Hirschfeld Further research involving possible pharmacological R, Fawcett J: Follow-up and family study of anxious depression. AmJ Psychiatry 1991; 148(11):1512-7 alternatives [e.g. adjunctive use of second-generation 16. Lebowitz BD, Pearson JL, Schneider LS, Reynolds CF, antipsychotic agents (36, 37)] as well as learning-based 3rd, Alexopoulos GS, Bruce ML, Conwell Y, Katz IR, Meyers BS, psychotherapies (like problem-solving therapy and cog- Morrison MF, Mossey J, Niederehe G, Parmelee P: Diagnosis and nitive-behavioral therapy [(38, 39)] is warranted. treatment of depression in late life. Consensus statement update. Jama1997; 278(14):1186-90 In conclusion, replicating and extending the 17. Charney DS, Reynolds CF, 3rd, Lewis L, Lebowitz BD, results of previous studies, our findings indicate a need Sunderland T, Alexopoulos GS, Blazer DG, Katz IR, Meyers BS, for active identification and aggressive treatment of Arean PA, Borson S, Brown C, Bruce ML, Callahan CM, Charlson anxiety symptoms in late-life depression, as well as the ME, Conwell Y, Cuthbert BN, Devanand DP, Gibson MJ, Gottlieb need for further research to identify optimal treatment.
GL, Krishnan KR, Laden SK, Lyketsos CG, Mulsant BH, NiedereheG, Olin JT, Oslin DW, Pearson J, Persky T, Pollock BG, Raetzman In order to improve outcomes in elderly patients with S, Reynolds M, Salzman C, Schulz R, Schwenk TL, Scolnick E, anxious depression, we need to develop and test treat- Unutzer J, Weissman MM, Young RC: Depression and Bipolar ment algorithms that would involve both psychosocial Support Alliance consensus statement on the unmet needs in diagno- and pharmacological alternative treatments. sis and treatment of mood disorders in late life. Arch Gen Psychiatry2003; 60(7):664-72 18. Reynolds CF, 3rd, Lebowitz BD: What are the best treat- REFERENCES
ments for depression in old age? Harv Ment Health Lett 1999;15(12):8 19. Reynolds CF, 3rd, Dew MA, Pollock BG, Mulsant BH, 1. Flint AJ: Epidemiology and comorbidity of anxiety disorders Frank E, Miller MD, Houck PR, Mazumdar S, Butters MA, Stack JA, in the elderly. Am J Psychiatry 1994; 151(5):640-9 Schlernitzauer MA, Whyte EM, Gildengers A, Karp J, Lenze E, 2. Kessler RC, Nelson CB, McGonagle KA, Liu J, Swartz M, Szanto K, Bensasi S, Kupfer DJ: Maintenance treatment of major Blazer DG: Comorbidity of DSM-III-R major depressive disorder in depression in old age. N Engl J Med 2006; 354(11):1130-8 the general population: results from the US National Comorbidity 20. Flint AJ, Rifat SL: Two-year outcome of elderly patients Survey. Br J Psychiatry Suppl 1996(30):17-30 with anxious depression. Psychiatry Res 1997; 66(1):23-31 3. Fava M AJ, Carmin CN, Wisniewski SR, Trivedi MH, BIggs 21. Zis AP GP, Webster M: Predictors of relapse in recurrent MM, Shores-Wilson K, Morgan D, Shwartz T, Balasubramani GK, affective disorders. Psychopharmacol Bull 1980; 16:47-49 Rush AJ: Clinical correlates and symptom patterns of anxious depres- 22. Reynolds CF, 3rd, Frank E, Perel JM, Miller MD, Cornes sion among patients with major depressive disorder in STAR*D.
C, Rifai AH, Pollock BG, Mazumdar S, George CJ, Houck PR, et al.: Psychological Medicine 2004; 34(7):1299-1308 Treatment of consecutive episodes of major depression in the elder- 4. Ben-Arie O, Swartz L, Dickman BJ: Depression in the eld- erly living in the community. Its presentation and features. Br J 23. Ganguli M, Belle S, Ratcliff G, Seaberg E, Huff FJ, von der 5. Beekman AT dBE, van Balkom AJ, Dorly JH Deeg, van Porten K, Kuller LH: Sensitivity and specificity for dementia of pop- Dyck R, van Tilburg W: Anxiety and depression in later life: co- ulation-based criteria for cognitive impairment: the MoVIES project.
occurence and communality of risk factors. Am J Psychiatry 2000; 24. Ganguli M, Dodge HH, Mulsant BH: Rates and predictors 6. Mulsant BH, Reynolds CF, 3rd, Shear MK, Sweet RA, of mortality in an aging, rural, community-based cohort: the role of Miller M: Comorbid anxiety disorders in late-life depression. Anxiety depression. Arch Gen Psychiatry 2002; 59(11):1046-52 25. First M SR, Gibbon M, Williams JBW: Structured clinical 7. Lenze EJ, Mulsant BH, Shear MK, Schulberg HC, Dew MA, interview for DSM-IV Axis I Disorders - Patient Edition (SCID-I/P).
Begley AE, Pollock BG, Reynolds CF, 3rd: Comorbid anxiety disorders in depressed elderly patients. Am J Psychiatry 2000; 157(5):722-8 26. Hamilton M: A rating scale for depression. J Neurol 8. Parmalee P KI, Lawton MD: Anxiety and its association with depression among institutionalized elderly. Am J Geriatr 27. Folstein MF, Folstein SE, McHugh PR: “Mini-mental state”. A practical method for grading the cognitive state of patients 9. Fawcett J: The detection and consequences of anxiety in for the clinician. Journal of Psychiatric Research 1975; 12(3):189-98 clinical depression. J Clin Psychiatry 1997; 58 Suppl 8:35-40 28. Klerman GL WM, Rounsaville BJ, Chevron E: 10. Flint AJ, Rifat SL: Anxious depression in elderly patients.
Interpersonal Psychotherapy of Depression. 1984 Response to antidepressant treatment. Am J Geriatr Psychiatry 1997; 29. Derogatis LR MN: The Brief Symptom Inventory: an intro- ductory report. Psychological Medicine 1983; 13:595-605 Revista Românã de Psihiatrie, seria a III-a, vol. IX, nr. 4, 2007 30. Buysse DJ, Reynolds CF, 3rd, Houck PR, Perel JM, Frank Hartford Center of Excellence in Geriatric Psychiatry,
E, Begley AE, Mazumdar S, Kupfer DJ: Does lorazepam impair the Department of Psychiatry, University of Pittsburgh School of
antidepressant response to nortriptyline and psychotherapy? J Clin Medicine; ** Center for Addiction and Mental Health, University
of Toronto, Canada; *** The Rotman Research Institute,
31. Gildengers AG, Houck PR, Mulsant BH, Dew MA, Baycrest Center for Geriatric Care, University of Toronto,
Aizenstein HJ, Jones BL, Greenhouse J, Pollock BG, Reynolds CF, 3rd: Trajectories of treatment response in late-life depression: psy-chosocial and clinical correlates. J Clin Psychopharmacol 2005; 25(4Suppl 1):S8-13 Acknowledgments: Supported by NIMH grants P30
32. Dombrovski AY MB, Houck PR, Mazumdar S, Lenze EJ, MH52247, P30 MH071944, R37 MH43832, K24 MH069430, R01
Andreescu C, Cyranowski JM, Reynolds CF: Impact of residual symp- MH37869 and Project EXPORT at the Center for Minority
toms on the risk of recurrence during maintenance treatment of late life Health, Graduate School of Public Health, University of
depression. American Journal of Geriatric Psychiatry 2006 (in press) Pittsburgh, NIH/NCMHD P60 MD-000-207; GlaxoSmithKline
33. Tyrer P, Seivewright H, Johnson T: The Nottingham donated supplies of paroxetine for the conduct of the research
Study of Neurotic Disorder: predictors of 12-year outcome of dys- reported here.
thymic, panic and generalized anxiety disorder. Psychol Med 2004; 34. Alexopoulos GS, Katz IR, Reynolds CF, 3rd, Carpenter D, Docherty JP, Ross RW: Pharmacotherapy of depression in older patients: a summary of the expert consensus guidelines. J Psychiatr 35. Baldwin DS, Polkinghorn C: Evidence-based pharma- Tel: 412 246 6007, Fax 412 246 6260.
cotherapy of Generalized Anxiety Disorder. Int JNeuropsychopharmacol 2005; 8(2):293-302 DECLARATION OF INTEREST
36. Adson DE, Kushner MG, Fahnhorst TA: Treatment of Carmen Andreescu, Mary Amanda Dew, Amy E. Begley, residual anxiety symptoms with adjunctive aripiprazole in depressed Alexandre Y. Dombrovski and Jacqueline Stack do not have any patients taking selective serotonin reuptake inhibitors. J AffectDisord 2005; 86(1):99-104 37. Wetherell JL, Lenze EJ, Stanley MA: Evidence-based Eric J. Lenze has received grant support from Forest treatment of geriatric anxiety disorders. Psychiatr Clin North Am Laboratories, Pfizer Inc., and Johnson & Johnson Co. Benoit H.
Mulsant has received honoraria and/or research support from Bristol- 38. Wetherell JL, Sorrell JT, Thorp SR, Patterson TL: Myers Squibb, Eli Lilly, Forest Laboratories, GlaxoSmithKline, Psychological interventions for late-life anxiety: a review and early Lundbeck, and Pfizer. Bruce G. Pollock has received honoraria lessons from the CALM study. J Geriatr Psychiatry Neurol 2005; and/or research support from Janssen Pharmaceutica, Forest Laboratories, GlaxoSmithKline, and Solvay and is on the speakers’ 39. Stanley MA, Beck JG, Novy DM, Averill PM, Swann AC, bureau for Forest Pharmaceuticals and Sepracor. Mark D. Miller is Diefenbach GJ, Hopko DR: Cognitive-behavioral treatment of late-life generalized anxiety disorder. J Consult Clin Psychol 2003; on the speakers’ bureau and also has been a consultant for Forest Pharmaceuticals and GlaxoSmithKline. Charles F. Reynolds III has From : * The Advanced Center for Interventions and
received research support from GlaxoSmithKline, Pfizer Inc., Eli Services Research for Late-life Mood Disorders and the John A.
Lilly and Co., Bristol Meyers Squibb, and Forest Pharmaceuticals.

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