Use of benzodiazepines and selective serotonin reuptake inhibitors in middle-aged and older adults with anxiety disorders: a longitudinal and prospective study. Controlled withdrawal of selective serotonin reuptake inhibitor drugs in elderly patients in nursing homes with no indication of depression Anti-depressants, suicide, and drug regulation. S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial. Response to an open trial of a second SSRI in major depression. Antidepressant Class, Age, and the Risk of Deliberate Self-Harm: A Propensity Score Matched Cohort Study of SSRI and SNRI Users in the USA Effects of antidepressant medication on morbidity and mortality in depressed patients after myocardial infarction. A randomised controlled trial of cognitive behaviour therapy in adolescents with major depression treated by selective serotonin reuptake inhibitors. The ADAPT trial. Treatment of selective serotonin reuptake inhibitor-resistant depression in adolescents: predictors and moderators of treatment response. Cardiac side‐effects of two selective serotonin reuptake inhibitors in middle- aged and elderly depressed patients A pragmatic 12-week, randomized trial of duloxetine versus generic selective serotonin-reuptake inhibitors in the treatment of adult outpatients in a moderate-to-severe depressive episode Effect of selective serotonin reuptake inhibitors on the risk of fracture. Antidepressants Reduce the Risk of Suicide among Elderly Depressed Patients Prophylactic efficacy of fluoxetine, escitalopram, sertraline, paroxetine, and concomitant psychotherapy in major depressive disorder: Outcome after long-term follow-up What happens with adverse events during 6 months of treatment with selective serotonin reuptake inhibitors? Cost-effectiveness of selective serotonin reuptake inhibitors and routine specialist care with and without cognitive behavioural therapy in adolescents with major depression. The impact of chronic depression on acute and long-term outcomes in a randomized trial comparing selective serotonin reuptake inhibitor monotherapy versus each of 2 different antidepressant medication combinations.
OBJECTIVE The purpose of this study was to examine the use of benzodiazepines ( BZs ) and selective serotonin reuptake inhibitors/selective norepinephrine reuptake inhibitors ( SSRIs/SNRIs ) over nine years of follow-up in middle-aged and older adults with diagnoses of panic disorder with or without agoraphobia , social phobia , or generalized anxiety disorder . SETTING AND PARTICIPANTS Participants in this study were enrolled in the Harvard/Brown Anxiety Research Project ( HARP ) . HARP is a naturalistic , longitudinal , multisite study of adults with anxiety disorders who are recruited from psychiatric setting s. The analytic sample consisted of 51 participants with anxiety disorders who were 55 to 70 years old at baseline and a younger cohort of 211 participants added for comparative analysis . DESIGN The authors examined patterns of medication use ( BZs and SSRIs/SNRIs ) in participants with anxiety disorders as they aged , by assessing the proportion of participants taking these medications using generalized estimating equation modeling . MEASUREMENTS The present data were derived from the structured diagnostic interview administered at enrollment using a combination of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders , Third Edition-R Non-Affective Disorder , Patient Version , Research Diagnostic Criteria Schedule for Affective Disorders-Lifetime , and subsequent follow-up interviews over a nine-year period using the Longitudinal Interval Follow-up Evaluation-Pharmacia & Upjohn to assess the weekly course of disorders to indicate syndrome severity and document medication use by specific type and dose on a weekly basis . RESULTS Findings showed that rates of BZ use were high among both the older ( 53 % at baseline ) and the younger ( 57.4 % ) age groups and did not significantly decrease over time , after controlling for time in episode of their anxiety disorders . There was a statistically significant increase in  SSRI/SNRI use over time in both groups . At the beginning of the study , 18 % of the older group and 21 % of the younger group were using SSRIs/SNRIs ; however , at the end of the study , the rates increased to 35 % and 43 % , respectively . CONCLUSIONS Although there was an increase in  SSRI/SNRI use in older participants with anxiety disorders over the course of study , at nine years of follow-up , only 35 % of participants were utilizing SSRI/SNRI medication , while more than one-half of the same participants were continuing to use BZs . To the authors ' knowledge , there are no r and omized clinical trials that have addressed comparative efficacy and safety of BZs and SSRIs/SNRIs in this population . However , there is documented evidence of adverse effects of chronic BZ use and the risk of developing dependency in older population Objective The aim of the investigation was to study the effects of withdrawing selective serotonin reuptake inhibitor ( SSRI ) drugs in nursing home patients , who had no documented diagnosis or symptoms of depression . Setting The setting of the study was in 11 nursing homes in the county of Stockholm , Sweden . Participants Participants were patients without dementia or history of depression who had received treatment with SSRI drugs for more than 6 months and who had no indications of anxiety disorder or major depression Design The included patients ( n=70 ) were r and omized to either the intervention group  ( withdrawal of SSRI ) or the control group  ( no change in treatment ) , 35 patients to each group . Main outcome measures The patients were subjected to assessment using the following instruments : Montgomery-Åsberg depression rating scale , global assessment for functioning , health index and a symptom assessment form . Assessment was made at the start of the study and at the 3-month and 6-month follow-ups . Results We found no significant difference between the intervention and control groups in any outcome measure . Conclusion Treatment with SSRI drugs in patients without clinical major depression or anxiety disorder is often unjustified and should be discontinued Policymakers are increasingly concerned that a relatively new class of anti-depressant drugs , selective serotonin re-uptake inhibitors ( SSRI ) , may increase the risk of suicide for at least some patients , particularly children . Prior r and omized trials are not informative on this question because of small sample sizes and other limitations . Using variation across countries over time in SSRI sales and suicide , we find that an increase of one pill per capita ( a 13 percent increase over 1999 levels ) is associated with a 2.5 percent reduction in suicide rates , a relationship that is more pronounced for adults than for children . Our findings suggest that exp and ing access to SSRIs for adults may be a cost-effective way to save lives , although policymakers are right to remain cautious about pediatric use of SSRIs OBJECTIVE Despite the progressive increase in the number of antidepressants , many patients with major depressive disorder continue to be symptomatic . Clearly , there is an urgent need to develop better tolerated and more effective treatments for this disorder . The use of S-adenosyl methionine ( SAMe ) , a naturally occurring molecule that serves as a methyl donor in human cellular metabolism , as adjunctive treatment for antidepressant nonresponders with major depressive disorder represents one such effort toward novel pharmacotherapy development . METHOD Participants were 73 serotonin reuptake inhibitor ( SRI ) nonresponders with major depressive disorder enrolled in a 6-week , double-blind , r and omized trial of adjunctive oral SAMe ( target dose : 800 mg/twice daily ) . Patients continued to receive their SRI treatment at a stable dose throughout the 6-week trial . The primary outcome measure for the study was the response rates according to the 17-item Hamilton Depression Rating Scale ( HAM-D ) . RESULTS The HAM-D response and remission rates were higher for patients treated with adjunctive SAMe ( 36.1 % and 25.8 % , respectively ) than adjunctive placebo ( 17.6 % versus 11.7 % , respectively ) . The number needed to treat for response and remission was approximately one in six and one in seven , respectively . There was no statistically significant difference in the proportion of SAMe- versus placebo-treated patients who discontinued the trial for any reason ( 20.6 % versus 29.5 % , respectively ) , due to adverse events ( 5.1 % versus 8.8 % , respectively ) , or due to inefficacy ( 5.1 % versus 11.7 % , respectively ) . CONCLUSIONS These preliminary results suggest that SAMe can be an effective , well-tolerated , and safe adjunctive treatment strategy for SRI nonresponders with major depressive disorder and warrant replication BACKGROUND We evaluated the efficacy of a second serotonin selective reuptake inhibitor ( SSRI ) in patients who had failed to respond to the first SSRI used . METHOD Fifty-five patients with major depression who had failed one of the SSRIs for their current depressive episode were included . After failing a trial of one SSRI , they received a second SSRI in an open clinical trial . RESULTS On the basis of the Clinical Global Impression-Improvement scale , 28 of 55 patients had a marked or complete antidepressant response . CONCLUSION These data provide preliminary clinical evidence that substituting a second SRI may be a useful clinical alternative in depressed patients who fail to respond to an adequate trial of an SSRI Background The US Food and Drug Administration ’s meta-analyses of placebo-controlled antidepressant trials found approximately twice the rate of suicidal behaviors among children and adults aged 24 years and younger who were r and omized to receive antidepressant medication  than among those who were r and omized to placebo .  Rates of suicidal behavior were similar for subjects aged 25–64 years whether they received antidepressants or placebo , and subjects aged 65 years or older r and omized to antidepressants were found to have lower rates of suicidal behavior . The age-stratified FDA meta-analyses did not have adequate power to investigate rates of suicidal behaviors by antidepressant drug class . Objective Our objective was to assess the risk of deliberate self-harm associated with the two most commonly prescribed classes of antidepressant agents . Design Propensity score matched cohort study of incident users of antidepressant agents . Setting Population -based healthcare utilization data of US residents . Patients US residents aged 10–64 years with a recorded diagnosis of depression who initiated use of selective serotonin reuptake inhibitors ( SSRIs ) or serotonin norepinephrine reuptake inhibitors ( SNRIs ) between 1 January 1998 and 31 December 2010.Main Outcome Measures ICD-9 external cause of injury codes E950.x – E958.x ( deliberate self-harm ) . Results A total of 102,647 patients aged between 10 and 24 years , and 338,021 aged between 25 and 64 years , initiated therapy with antidepressants . Among 10–24 year olds , prior to propensity score matching , 75,675 initiated therapy with SSRIs and 5,344 initiated SNRIs . After matching , there were 5,344 SNRI users and 10,688 SSRI users . Among the older cohort , 36,037 SNRI users were matched to 72,028 SSRI users ( from an unmatched cohort of 225,952 SSRI initiators ) . Regardless of age cohort , patients initiating SSRIs and patients initiating SNRIs had similar rates of deliberate self-harm . Restriction to patients with no antidepressant use in the past 3 years did not alter our findings . Conclusions Our findings of similar rates of deliberate self-harm for depressed patients who initiate treatment with either an SSRI or an SNRI suggests that physicians who have decided that their patients would benefit from initiating antidepressant therapy need not weigh differential suicide risk when deciding which class of antidepressant to prescribe BACKGROUND Depression after myocardial infa rct ion ( MI ) is associated with higher morbidity and mortality . Although antidepressants are effective in reducing depression , their use in patients with cardiovascular disease remains controversial . OBJECTIVE To undertake a secondary analysis to determine the effects of using antidepressants on morbidity and mortality in post-MI patients who participated in the Enhancing Recovery in Coronary Heart Disease study . DESIGN Observational secondary analysis . SETTING Eight academic sites . PATIENTS The Enhancing Recovery in Coronary Heart Disease clinical trial r and omized 2481 depressed and /or socially isolated patients from October 1 , 1996 , to October 31 , 1999 . Depression was diagnosed using a structured clinical interview . This analysis was conducted on the 1834 patients enrolled with depression ( 849 women and 985 men ) . INTERVENTION Use of antidepressant medication . MAIN OUTCOME MEASURES Event-free survival was defined as the absence of death or recurrent MI . All-cause mortality was also examined . To relate exposure to antidepressants to subsequent morbidity and mortality , the data were analyzed using a time-dependent covariate model . RESULTS During a mean follow-up of 29 months , 457 fatal and nonfatal cardiovascular events occurred . The risk of death or recurrent MI was significantly lower in patients taking selective serotonin reuptake inhibitors ( adjusted hazard ratio [ HR ] , 0.57 ; 95 % confidence interval [ CI ] , 0.38 - 0.84 ) , as were the risk of all-cause mortality ( adjusted HR , 0.59 ; 95 % CI , 0.37 - 0.96 ) and recurrent MI ( adjusted HR , 0.53 ; 95 % CI , 0.32 - 0.90 ) , compared with patients who did not use selective serotonin reuptake inhibitors . For patients taking non-selective serotonin reuptake inhibitor antidepressants , the comparable HRs ( 95 % CIs ) were 0.72 ( 0.44 - 1.18 ) , 0.64 ( 0.34 - 1.22 ) , and 0.73 ( 0.38 - 1.38 ) for risk of death or recurrent MI , all-cause mortality , or recurrent MI , respectively , compared with nonusers . CONCLUSIONS Use of selective serotonin reuptake inhibitors in depressed patients who experience an acute MI might reduce subsequent cardiovascular morbidity and mortality . A controlled trial is needed to examine this important issue OBJECTIVES To determine if , in the short term , depressed adolescents attending routine NHS Child and Adolescent Mental Health Services ( CAMHS ) , and receiving ongoing active clinical care , treatment with selective serotonin reuptake inhibitors ( SSRIs ) plus cognitive behaviour therapy ( CBT ) compared with SSRI alone , results in better healthcare outcomes . DESIGN A pragmatic r and omised controlled trial ( RCT ) was conducted on depressed adolescents attending CAMHS who had not responded to a psychosocial brief initial intervention ( BII ) prior to r and omisation . SETTING Six English CAMHS participated in the study . PARTICIPANTS A total of 208 patients aged between 11 and 17 years were recruited and r and omised . INTERVENTIONS All participants received active routine clinical care in a CAMHS outpatient setting and an SSRI and half were offered CBT . MAIN OUTCOME MEASURES The duration of the trial was a 12-week treatment phase , followed by a 16-week maintenance phase . Follow-up assessment s were at 6 , 12 and 28 weeks . The primary outcome measure was the Health of the Nation Outcome Scales for Children and Adolescents ( HoNOSCA ) . Secondary outcome measures were self-report depressive symptoms , interviewer-rated depressive signs and symptoms , interviewer-rated psychosocial impairment and clinical global impression of response to treatment . Information on re source use was collected in interview at baseline and at the 12- and 28-week follow-up assessment s using the Child and Adolescent Service Use Schedule ( CA-SUS ) . RESULTS Of the 208 patients r and omised , 200 ( 96 % ) completed the trial to the primary end-point at 12 weeks . By the 28-week follow-up , 174 ( 84 % ) participants were re-evaluated . Overall , 193 ( 93 % ) participants had been assessed at one or more time points . Clinical characteristics indicated that the trial was conducted on a severely depressed group . There was significant recovery at all time points in both arms . The findings demonstrated no difference in treatment effectiveness for SSRI + CBT over SSRI only for the primary or secondary outcome measures at any time point . This lack of difference held when baseline and treatment characteristics where taken into account ( age , sex , severity , co-morbid characteristics , quality and quantity of CBT treatment , number of clinic attendances ) . The SSRI + CBT group was somewhat more expensive over the 28 weeks than the SSRI-only group ( p=0.057 ) and no more cost-effective . Over the trial period there was on average a decrease in suicidal thoughts and self-harm compared with levels recorded at baseline . There was no significant increase in disinhibition , irritability and violence compared with levels at baseline . Around 20 % ( n=40 ) of patients in the trial were non-responders . Of these , 17 ( 43 % ) showed no improvement by 28 weeks and 23 ( 57 % ) were considered minimally ( n=10 ) or moderately to severely worse ( n=13 ) . CONCLUSIONS For moderately to severely depressed adolescents who are non-responsive to a BII , the addition of CBT to fluoxetine plus routine clinical care does not improve outcome or confer protective effects against adverse events and is not cost-effective . SSRIs ( mostly fluoxetine ) are not likely to result in harmful adverse effects . The findings are broadly consistent with existing guidelines on the treatment of moderate to severe depression . Modification is advised for those presenting with moderate ( 6 - 8 symptoms ) to severe depressions ( > 8 symptoms ) and in those with either overt suicidal risk and /or high levels of personal impairment . In such cases , the time allowed for response to psychosocial interventions should be no more than 2 - 4 weeks , after which fluoxetine should be prescribed . Further research should focus on evaluating the efficacy of specific psychological treatments against brief psychological intervention , determining the characteristics of patients with severe depression who are non-responsive to fluoxetine , relapse prevention in severe depression and improving tools for determining treatment responders and non-responders OBJECTIVE To advance knowledge regarding strategies for treating selective serotonin reuptake inhibitor (SSRI)-resistant depression in adolescents , we conducted a r and omized controlled trial evaluating alternative treatment strategies . In primary analyses , cognitive-behavioral therapy ( CBT ) combined with medication change was associated with higher rates of positive response to short-term ( 12-week ) treatment than medication alone . This study examines predictors and moderators of treatment response , with the goal of informing efforts to match youths to optimal treatment strategies . METHOD Youths who had not improved during an adequate SSRI trial ( N = 334 ) were r and omized to an alternative SSRI , an alternative SSRI plus CBT , venlafaxine , or venlafaxine plus CBT . Analyses examined predictors and moderators of treatment response . RESULTS Less severe depression , less family conflict , and absence of nonsuicidal self-injurious behavior predicted better treatment response status . Significant moderators of response to CBT + medication ( combined ) treatment were number of comorbid disorders and abuse history ; hopelessness was marginally significant . The CBT/combined treatment superiority over medication alone was more evident among youths who had more comorbid disorders ( particularly attention-deficit/hyperactivity disorder and anxiety disorders ) , no abuse history , and lower hopelessness . Further analyses revealed a stronger effect of combined CBT + medication treatment among youths who were older and white and had no nonsuicidal self-injurious behavior and longer pre study pharmacotherapy . CONCLUSIONS Combined treatment with CBT and antidepressant medication may be more advantageous for adolescents whose depression is comorbid with other disorders . Given the additional costs of adding CBT to medication , consideration of moderators in clinical decision making can contribute to a more personalized and effective approach to treatment Selective serotonin reuptake inhibitors ( SSRIs ) are the ‘ new ’ drugs of first choice for the treatment of depression in the older patient . Systematic studies on the effects of SSRIs on cardiac function are scarce , despite the high prevalence of cardiac disorders in the older depressed patient . This is a study which systematic ally assesed cardiac function by echo-cardiography in middle-aged and elderly depressed patients treated with SSRI . In a double-blind r and omized trial , 20 patients were assigned to receive fluvoxamine 20 mg/day or fluoxetine 100mg/day for 6 weeks . Cardiac function was assessed by left ventricle ejection fraction , aortic flow integral and early or passive/late or active mitral inflow , and electrocardiography . Neither SSRI significantly affected cardiac function . Compared with patients without a history of myocardial infa rct ion and /or hypertension , patients with such a history showed a significant improvement in left ventricular ejection fraction . Despite our small study sample , these data indicate that both fluoxetine and fluvoxamine do not affect cardiac function adversely Some evidence suggests that medications that modulate both serotonin and norepinephrine may be more effective than selective serotonin-reuptake inhibitors ( SSRIs ) in severe major depressive disorder ( MDD ) . This prospect i ve pragmatic trial tests this hypothesis . Patients with severe MDD were r and omly assigned to either duloxetine ( a serotonin and norepinephrine-reuptake inhibitor ) or physicians ’ choice of four generic SSRIs . Nonblinded , flexibly dosed treatment was used to mimic clinical practice . To address potential investigator bias , the patient-reported Quick Inventory of Depressive Symptomatology Self-Report ( QIDS-SR ) was used as the primary efficacy outcome measure . A total of 750 out patients ( 19.2 % , African descent ; 14.8 % , Hispanic ) were r and omized . The primary outcome , remission at week 12 by QIDS-SR , was numerically greater for duloxetine compared with SSRIs ( 36 vs. 32 % ) , but this difference was not statistically significant . Mean changes in secondary outcomes were significantly superior in favor of duloxetine for the Hamilton Depression Scale-17 item , the Brief Pain Inventory , and the Sheehan Disability Scale . Remission superiority on the QIDS-SR was not achieved . Significantly greater benefit for duloxetine compared with SSRIs was demonstrated on measures of pain and functioning . Study demographics suggest a more generalizable racial and ethnic population than is typical in r and omized clinical trials BACKGROUND Depression and osteoporotic fractures are common ailments among elderly persons .  Selective serotonin reuptake inhibitors ( SSRIs ) are frequently used in the treatment of depression in this population , and the association between daily SSRI use and fragility fractures is unclear . Our objective was to examine the effect of daily SSRI use on the risk of incident clinical fragility fracture . METHODS A population -based , r and omly selected , prospect i ve cohort study of 5008 community-dwelling adults 50 years and older , followed up over 5 years for incident fractures . Clinical fragility fractures were classified as minimal trauma fractures that were clinical ly reported and radiographically confirmed . The risk of fragility fracture associated with daily SSRI use was determined while controlling for relevant covariates . RESULTS Daily SSRI use was reported by 137 subjects . After adjustment for many potential covariates , daily SSRI use was associated with substantially increased risk of incident clinical fragility fracture ( hazard rate , 2.1 ; 95 % confidence interval , 1.3 - 3.4 ) . Daily SSRI use was also associated with increased odds of falling ( odds ratio , 2.2 ; 95 % confidence interval , 1.4 - 3.5 ) , lower bone mineral density at the hip , and a trend toward lower bone mineral density at the spine . These effects were dose dependent and were similar for those who reported taking SSRIs at baseline and at 5 years ' follow-up . CONCLUSIONS Daily SSRI use in adults 50 years and older remained associated with a 2-fold increased risk of clinical fragility fracture after adjustment for potential covariates . Depression and fragility fractures are common in this age group , and the elevated risk attributed to daily SSRI use may have important public health consequences Treatment 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 SSRIs in the elderly may be beneficial . We aim ed to evaluate the association between 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 period . 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 admission 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 from MDD who were hospitalized following a suicide attempt . Mean age for the group was 76.5±6.6 years ; there were 42 men and 59 women . The control group patients ( N=101 ) were matched for age ( mean 76.6±6.9 years ) and sex . The proportion of patients exposed to an antidepressant  was significantly greater in the control group , than in the group of patients who had attempted suicide ( 58 vs 42 % , odds ratio 1.94 ( 95 % CI : 1.1–3.4 ) , p=0.019 ) . SSRIs were prescribed in 29 % of patients in the control group vs 21 % of patients in the index group ( p=0.03 ) . 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 attempting suicide . These findings need support from prospect i ve r and omized trials The acute efficacy of selective serotonin reuptake inhibitors ( SSRIs ) in the treatment of major depressive disorder ( MDD ) is well established ; however their role in longer-term prevention of recurrence remains unconfirmed . This study aims at examining : the prophylactic efficacy of four commonly used SSRIs in MDD in a naturalistic setting with long-term follow-up , the effect of concomitant cognitive behavioral therapy ( CBT ) , and the predictors of outcome . In a prospect i ve cohort study , 387 patients who either remitted or responded following treatment with four different SSRIs-fluoxetine , escitalopram , sertraline and paroxetine-were  followed up over several years . During an average follow-up period of 34.5 months , 76.5 % of patients experienced MDD recurrence . Escitalopram and fluoxetine showed a numerically higher prophylactic efficacy than paroxetine and sertraline but the difference was statistically insignificant . The prophylactic efficacy for SSRI-only treatment was limited , with a recurrence rate of 82.0 % , compared to 59.0 % of patient recurrence rate in concomitant Cognitive Behavioral Therapy ( CBT ) . The relatively small size of the CBT group and the lack of r and omization may undermine the extrapolation of its findings to clinical practice . Nevertheless , the study preliminary data may help in defining the clinical utility of antidepressants and CBT in the prophylaxis from MDD recurrence OBJECTIVE Although adverse events are a key factor in compliance , their evolution during treatment with antidepressants is poorly documented . Therefore , the time course of adverse events during 6 months of antidepressant treatment was investigated . METHOD 85 psychiatric out patients with a DSM-IV diagnosis of major depressive disorder ( with the exclusion of other DSM-IV Axis I disorders ) were enrolled between September 2002 and March 2003 in a multicenter , r and omized , double-blind trial with selective serotonin reup-take inhibitors ( fluoxetine [ N = 42 ] and paroxetine [ N = 43 ] ) . At each visit , the presence and severity of treatment-emergent adverse events were assessed systematic ally using the UKU Side Effect Rating Scale ( UKU ) . General linear mixed modeling was used to investigate the predictors of the time course of adverse events . RESULTS Overall , the number of at least moderately severe adverse events decreased with time . More severely depressed patients reported overall more ( at least moderately severe ) adverse events than less severely depressed patients ( p = .0002 ) , but the decrease in reported adverse events was comparable over time . Men ( N = 30 ) and women ( N = 55 ) reported initially the same number of at least moderately severe adverse events , but the habituation was more rapid in men ( p < .0001 ) . Completers ( N = 58 ) and dropouts ( N = 27 ) did not differ initially , but completers ' habituation was more rapid ( p = .014 ) . The habituation of adverse events was also more rapid in recurrent than in first-episode patients but only in men ( p = .0025 ) . CONCLUSION The time course of adverse events varies with the severity of depression , sex , completer or dropout status , and recurrent versus first-episode depression BACKGROUND Major depression is an important and costly problem among adolescents , yet evidence to support the provision of cost-effective treatments is lacking . AIMS To assess the short-term cost-effectiveness of combined selective serotonin reuptake inhibitors ( SSRIs ) and cognitive-behavioural therapy ( CBT ) together with clinical care compared with SSRIs and clinical care alone in adolescents with major depression . METHOD Pragmatic r and omised controlled trial in the UK .  Outcomes and costs were assessed at baseline , 12 and 28 weeks . RESULTS The trial comprised 208 adolescents , aged 11 - 17 years , with major or probable major depression who had not responded to a brief initial psychosocial intervention . There were no significant differences in outcome between the groups with and without CBT .  Costs were higher in the group with CBT , although not significantly so ( P=0.057 ) . Cost-effectiveness analysis and exploration of the associated uncertainty suggest there is less than a 30 % probability that CBT plus SSRIs is more cost-effective than SSRIs alone . CONCLUSIONS A combination of CBT plus SSRIs is not more cost-effective in the short-term than SSRIs alone for treating adolescents with major depression in receipt of routine specialist clinical care OBJECTIVE To compare sociodemographic and clinical features , acute and continuation treatment outcomes , and adverse events/side effect burden between out patients with chronic ( current episode > 2 years ) versus nonchronic major depressive disorder ( MDD ) who were treated with combination antidepressant therapy or selective serotonin reuptake inhibitor ( SSRI ) monotherapy . METHOD 663 out patients with chronic ( n = 368 ) or nonchronic ( n = 295 ) moderate to severe DSM-IV-TR MDD ( 17-item Hamilton Depression Rating Scale score ≥ 16 ) were enrolled from March 2008 through September 2009 in a single-blind 7-month prospect i ve r and omized trial conducted at 6 primary and 9 psychiatric care sites across the United States . Participants were treated with escitalopram monotherapy plus placebo or 1 of 2 combination treatments ( bupropion sustained-release [ SR ] + escitalopram or venlafaxine extended-release [ XR ] + mirtazapine ) . Analyses compared baseline sociodemographic and clinical characteristics , rates of remission ( at least 1 of the last 2 consecutive scores on the 16-item Quick Inventory of Depressive Symptomatology-Self-Report [ QIDS-SR16 ] < 6 , with the other < 8) , and adverse events/side effect burden ( Frequency , Intensity , and Burden of Side Effects Ratings ) obtained at 12 and 28 weeks . RESULTS Participants with chronic MDD were at greater socioeconomic disadvantage and had greater medical and psychiatric disease burden  . The chronic and nonchronic groups did not differ in rates of remission at 12 weeks ( 35.9 % vs 42.0 % , respectively ; odds ratio [ OR ] = 0.778 , P = .1500 ; adjusted OR [ AOR ] = 0.956 , P = .8130 ) or at 28 weeks ( 41.0 % vs 49.8 % , respectively ; OR = 0.706 , P = .0416 ; AOR = 0.837 , P = .3448 ) . Participants with chronic MDD had higher final QIDS-SR(16 ) scores and smaller overall percent changes in QIDS-SR(16 ) from baseline to exit , but these differences did not remain after adjusting for covariates . There were no significant differences in adverse events or side effect burden . No significant interactions were found between chronicity and type of treatment at 12 or 28 weeks . CONCLUSION Chronicity of illness does not appear to differentially impact acute or longer-term outcomes with SSRI monotherapy or combination antidepressant medication treatment in patients with moderate to severe nonpsychotic MDD . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00590863
After having corrected for these apparent mistakes , we conducted a sensitivity analysis in which we also accounted for a possible moderating effect of age ; while this suggests SSRIs to be safe drugs in the non-elderly , they do confirm what is already known , that is , that they may enhance the risk for SAEs in the old .
According to a systematic review on the use of selective serotonin reuptake inhibitors ( SSRIs ) in adult depression that was recently published in BMC Psychiatry , the results of which have been widely disseminated in lay media , these drugs increase the risk for serious adverse events ( SAEs ) while exerting poor antidepressant efficacy .