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Recent research: five studies on depression – including side-effects, young people, heart attacks, and bipolar disorder

Here are the abstracts of five recent research studies on depression and antidepressants.  The first confirms earlier work showing an increased risk of gastrointestinal bleeding with SSRI's (particularly if also taking NSAID's).  The second highlights the potential physical survival value of screening for and treating depression in people who have suffered a heart attack.  The third and fifth discuss the limited benefits and the limited risks of using antidepressants with young people.  The fourth study highlights the potential protective value of encouraging 'social rhythm regularity' in people suffering from cyclothymia and bipolar II disorder. 

de Abajo, F. J. and L. A. Garcia-Rodriguez (2008). "Risk of Upper Gastrointestinal Tract Bleeding Associated With Selective Serotonin Reuptake Inhibitors and Venlafaxine Therapy: Interaction With Nonsteroidal Anti-inflammatory Drugs and Effect of Acid-Suppressing Agents." Arch Gen Psychiatry 65(7): 795-803.  [Abstract/Full Text]  
Context Selective serotonin reuptake inhibitors have been reported to increase the risk of upper gastrointestinal tract bleeding. The wide use of these drugs makes such potential risk a public health concern, and identification of factors that may increase or minimize such risk is necessary. Objectives To test the association of selective serotonin reuptake inhibitors and venlafaxine hydrochloride therapy with upper gastrointestinal tract bleeding, to identify subgroups of patients at particularly increased risk, and to explore whether acid-suppressing agents may be effective in minimizing risk. Design Nested case-control study. Setting General practice database from the United Kingdom. Participants One thousand three hundred twenty-one patients with upper gastrointestinal tract bleeding referred to a consultant or hospital and 10 000 control subjects matched for age, sex, and calendar year of the index date. Main Outcome Measure Risk of bleeding associated with selective serotonin reuptake inhibitors and effect of acid-suppressing agents. Results The percentage of current users of selective serotonin reuptake inhibitors (5.3%) or venlafaxine (1.1%) among case subjects was significantly higher than in matched control subjects (3.0% and 0.3%; adjusted odds ratio [OR], 1.6; 95% confidence interval [CI], 1.2-2.1, and OR, 2.9; 95% CI, 1.5-5.6, respectively). An interaction with nonsteroidal anti-inflammatory drugs (OR, 4.8; 95% CI, 2.8-8.3) was observed, in particular among those not using acid-suppressing agents (OR, 9.1; 95% CI, 4.8-17.3) compared with users of these drugs (OR, 1.3; 95% CI, 0.5-3.3). In addition, an interaction with antiplatelet drugs in nonusers of acid-suppressing agents was suggested (OR, 4.7; 95% CI, 2.6-8.3) compared with users of these drugs (OR, 0.8; 95% CI, 0.3-2.5). Conclusions Antidepressants with a relevant blockade action on the serotonin reuptake mechanism increase the risk of upper gastrointestinal tract bleeding. The increased risk may be of particular relevance when these drugs are associated with nonsteroidal anti-inflammatory drugs. Our study findings also provide evidence that use of acid-suppressing agents limits such increased risk.

Huffman, J. C., F. A. Smith, et al. (2008). "Pre-Existing Major Depression Predicts In-Hospital Cardiac Complications After Acute Myocardial Infarction." Psychosomatics 49(4): 309-316.   [Abstract/Full Text]  
BACKGROUND: Depression (MDD) and anxiety have been associated with negative long-term outcomes among patients with acute myocardial infarction (MI). OBJECTIVE: The objective of the study was to determine whether MDD and anxiety preceding MI were associated with in-hospital post-MI cardiac complications. METHOD: Subjects (N=129) underwent psychiatric interviews within 72 hours of MI and were evaluated for five in-hospital cardiac complications (recurrent ischemia, ventricular arrhythmia, ventricular arrhythmia requiring intervention, congestive heart failure, and reinfarction). RESULTS: Current (pre-MI) MDD was a significant and independent predictor of all complications except recurrent ischemia on multivariate regression analysis. In contrast, pre-MI anxiety was not associated with complications. CONCLUSION: These findings underscore the importance of identifying and treating MDD in post-MI patients and those at risk for MI.

Moller, H. J., D. S. Baldwin, et al. (2008). "Do SSRIs or antidepressants in general increase suicidality? WPA Section on Pharmacopsychiatry: consensus statement." Eur Arch Psychiatry Clin Neurosci 258 Suppl 3: 3-23.   [PubMed]  
In the past few years several papers have reported critically on the risk of suicidal thoughts and behaviour associated with antidepressants, primarily SSRIs. The risk-benefit ratio of antidepressant (AD) treatment has been questioned especially in children and adolescents. The critical publications led to warnings being issued by regulatory authorities such as the FDA, MHRA and EMEA and stimulated new research activity in this field. However, potential harmful effects of antidepressants on suicidality are difficult to investigate in empirical studies because these have several methodological limitations. Randomised controlled trials (RCTs) are the most reliable way to test the hypothesis that AD have such side effects. In addition to meta-analyses of RCTs, complementary research methods should be applied to obtain the most comprehensive information. We undertook a comprehensive review of publications related to the topics ADs, suicide, suicidality, suicidal behaviour and aggression. Based on this comprehensive review we conclude that ADs, including SSRIs, carry a small risk of inducing suicidal thoughts and suicide attempts, in age groups below 25 years, the risk reducing further at the age of about 30-40 years. This risk has to be balanced against the well-known beneficial effects of ADs on depressive and other symptoms (anxiety, panic, obsessive-compulsive symptoms), including suicidality and suicidal behaviour. According to the principles of good clinical practice, decision making should consider carefully the beneficial effects of AD treatment as well as potentially harmful effects and attempt to keep the potential risks of AD treatment to a minimum. It is the major problem facing efforts to identify the possible 'suicidal effects' of antidepressants.

Shen, G. H., L. B. Alloy, et al. (2008). "Social rhythm regularity and the onset of affective episodes in bipolar spectrum individuals." Bipolar Disorders 10(4): 520-529.   [Abstract/Full Text]
Research suggests that bipolar disorder individuals may have less social rhythm regularity than normal controls and that this may contribute to their affective symptoms and episodes. This study examined whether regularity prospectively predicted time to onset of major depressive, hypomanic and manic episodes in a sample with bipolar spectrum disorders.Methods:  We recruited 414 undergraduate students from Temple University and University of Wisconsin diagnosed with cyclothymia, bipolar II disorder, or with no affective disorder (normal controls). Participants completed the Social Rhythm Metric at Time 1 and structured interviews approximately every four months for an average follow-up period of 33 months.Results:  Participants diagnosed with cyclothymia and bipolar II disorder reported significantly fewer regular activities than normal controls, and approximately half of these participants experienced a worsening course of their illness over the study duration. Survival analyses indicated that both diagnosis and social rhythm regularity significantly predicted the time to participants' first prospective onset of major depressive, hypomanic and manic episodes.Conclusion:  Consistent with the social zeitgeber theory, bipolar spectrum participants reported less social rhythm regularity than normal controls, which prospectively predicted the survival time to affective episodes.

Tsapakis*, E. M., F. Soldani*, et al. (2008). "Efficacy of antidepressants in juvenile depression: meta-analysis." The British Journal of Psychiatry 193(1): 10-17.  [Abstract/Full Text]   
Background The safety of antidepressants in children and adolescents is being questioned and the efficacy of these drugs in juvenile depression remains uncertain. Aims To assess antidepressant efficacy in juvenile depression. Method Systematic review and meta-analysis of randomised controlled trials (RCTs) comparing responses to antidepressants, overall and by type, v. placebo in young people with depression. Results Thirty drug-placebo contrasts in RCTs lasting 8 weeks (median) involved 3069 participants (512 person-years) of average age 13.5 years. Meta-analysis yielded a modest pooled drug/placebo response rate ratio (RR=1.22, 95% CI 1.15-1.31), with little separation between antidepressant types. Findings were similar for response rate differences and corresponding number needed to treat (NNT): overall NNT=9; tricyclic antidepressants NNT=14 > serotonin reuptake inhibitors NNT=9 > other antidepressants NNT=8. Numbers needed to treat decreased with increasing age: children (NNT=21) > mixed ages (NNT=10) > adolescents (NNT=8). Conclusions Antidepressants of all types showed limited efficacy in juvenile depression, but fluoxetine might be more effective, especially in adolescents. Studies in children and in severely depressed, hospitalised or suicidal juvenile patients are needed, and effective, safe and readily accessible treatments for juvenile depression are urgently required.

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