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on depression ISSUE 2, 2015
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MAJOR DEPRESSIVE DISORDER AND SMOkING
RELAPSE AMONG ADULTS IN THE UNITED STATES:
A 10-YEAR, PROSPECTIVE INVESTIGATION
Psychiatry Research, 2015 March 30; 226(1):73–7 AUTHORS: Zvolensky MJ, Bakhshaie J, Sheffer C, Perez A, Goodwin RDCENTRES: Department of Psychology, University of Houston; and Department of Behavioral Sciences, University of Texas MD Anderson Cancer Center, Houston, Texas; Sophie Davis School of Biomedical Education, City College of New York; Department of Psychology, Queens College and The Graduate Center, City University of New York (CUNY), Queens; and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA BACkGROUND & AIM: Cigarette smok-
METHOD: Data from adult participants
ing is the major preventable cause of death in the Midlife Development in the United in the USA. Although most smokers would States (MIDUS) Survey Waves I & II were like to stop smoking, the quit rate remains analysed using logistic regression to explore low. It would therefore be helpful to iden- associations between MDD in 1994, MDD tify modifiable risk factors for smoking in 2005 and persistent depression (in 1994 relapse among former smokers. Epidemio- and 2005) and risk of smoking relapse in logical evidence suggests a link between 2005 among former smokers, adjusting for current or past depression and poor smok- demographics, anxiety disorders, substance ing cessation outcomes, but the degree to use problems and smoking characteristics. which depression affects the long-term risk of smoking relapse, and the influence of the RESULTS: Among former smokers, adults
proximity and persistence of depression on with depression in 1994 (n=91) were sig- risk of relapse, remain to be determined. nificantly more likely than those without The aim of this study was to determine depression in 1994 (n=608) to experience the association between a history of major smoking relapse by 2005 (adjusted odds depressive disorder (MDD) and the long- ratio 2.4, 95% confidence interval 1.3–4.2, term risk of smoking relapse among former p<0.05). The risk of smoking relapse in smokers in the general US population. The 2005 was also significantly (p<0.05) higher relation between current and persistent among adults with current depression in depression and risk of relapse among for- 2005 (n=77) than among those without cur- mer smokers compared to those without rent depression (n=622; adjusted OR 3.3, depression was also explored.
95% 1.8–6.0) and among those with per-sistent depression (n=25) than among those STUDY DESIGN: Cohort study.
with no depression in either 1994 or 2005 (n=556; adjusted OR 3.5, 95% CI 1.3–9.4). ENDPOINTS: Relationships between:
depression in 1994 and risk of smoking
CONCLUSION: MDD was associated with
relapse by 2005; depression in 2005 and both a short- and long-term increased risk risk of smoking relapse by 2005; and persis- of smoking relapse among former smokers tent depression (in 1994 and 2005) and risk in the US general population.
of smoking relapse by 2005.
IMPACT OF CHILDHOOD LIFE EVENTS
AND CHILDHOOD TRAUMA
ON THE ONSET AND RECURRENCE OF DEPRESSIVE
AND ANXIETY DISORDERS
The Journal of Clinical Psychiatry, 2015 February 17; Epub ahead of print AUTHORS: Hovens JG, Giltay EJ, Spinhoven P, van Hemert AM, Penninx BWCENTRES: Department of Psychiatry, Leiden University Medical Center, Leiden; Institute of Psychology, Leiden University, Leiden; VU University Medical Center, Amsterdam; and Department of Psychiatry, University Medical Center Groningen, Groningen, the Netherlands BACkGROUND & AIM: Adverse experi-
least one childhood life event and 412 ences in childhood have been associated (35.3%) reported a history of any child- with psychopathology such as depressive hood trauma. At 2-year follow up, 226 and anxiety disorders in later life. However, participants (19.4%) were diagnosed with prospective evidence for these associations a new (n=58) or recurrent (n=168) episode is scarce. The aim of this study was to of a depressive and/or anxiety disorder. First investigate the effect of childhood life events onset or recurrence of either a depressive and trauma on the onset and recurrence of or comorbid disorder, but not an anxiety depressive and/or anxiety disorders over a disorder, was significantly higher among 2-year period in participants without cur- individuals who had experienced child- rent psychopathology at baseline.
hood emotional neglect or psychological, physical or sexual abuse (p<0.001). On STUDY DESIGN: Prospective cohort study.
multivariate analysis, emotional neglect was the only significant independent predictor ENDPOINTS: Associations of childhood
of first onset or recurrence of any depres- life events (death of a parent, divorce of sive or comorbid disorder (p=0.002). Severe parents, being placed in care) or childhood psychological and sexual abuse were both trauma (emotional neglect and psychologi- predictive of the occurrence of a comor- cal, physical or sexual abuse) with 2-year bid disorder (p<0.05). These effects were occurrence rates of new or recurrent depres- primarily mediated by the severity of (sub- sive and/or anxiety disorders.
clinical) depressive symptoms at baseline (mediating effect 0.117, 95% confidence METHOD: Longitudinal data were col-
interval 0.077–0.173) and a prior lifetime lected from 1167 adults participating in the diagnosis of a depressive and/or anxiety Netherlands Study of Depression and Anxi- disorder (mediating effect 0.072, 95% CI ety who had no depressive or anxiety dis- 0.042–0.108). Childhood life events did not order at baseline (2004–2007). Depressive predict the onset or recurrence of depressive and/or anxiety disorders emerging during 2 or anxiety disorders.
years of follow-up were diagnosed using the Composite International Diagnostic Inter- CONCLUSION: Childhood trauma was
view. Factors associated with the incidence found to predict the occurrence of depres- of these disorders were identified using a sive and comorbid disorders within 2 years multivariable logistic regression model.
in adults without current psychopathology at baseline.
RESULTS: At baseline, 172 (14.7%) par-
ticipants reported having experienced at
EFFECTS OF ADJUNCTIVE EXERCISE
ON PHYSIOLOGICAL AND PSYCHOLOGICAL
PARAMETERS IN DEPRESSION:
A RANDOMIZED PILOT TRIAL
Journal of Affective Disorders, 2015 May 15; 177:1–6 AUTHORS: Kerling A, Tegtbur U, Gützlaff E, Kück M, Borchert L, Ates Z, von Bohlen A, Frieling H,Hüper K, Hartung D, Schweiger U, Kahl KGCENTRE FOR CORRESPONDENCE: Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany BACkGROUND & AIM: Depressed indi-
randomized to receive treatment as usual viduals show reduced physical activity and only (TAU group, n=20) or combined with increased rates of the metabolic syndrome physician-supervised exercise training for (MetS), a risk factor for type 2 diabetes and 6 weeks (exercise group, n=22). Exercise cardiovascular disorders. Exercise training training consisted of three 45-minute ses- has been shown to improve cardiorespira- sions of moderate-intensity exercise per tory fitness and MetS factors, and to have week. MetS was defined according to the a moderate effect on depressive symptoms. National Cholesterol Education Program's However, exercise prescription to depressive Adult Treatment Panel III criteria. patients is challenging, and the feasibility of exercise interventions for severely depressed RESULTS: Depressive symptoms declined
patients in an inpatient setting is unclear. significantly in both groups during the study The aims of this study were to evaluate period. However, more patients in the exer- the feasibility of an exercise intervention cise group than the TAU group were classi- and its effects on depressive symptoms, fied as responders at 6 weeks (14 versus 6, cardiorespiratory fitness and MetS compo- p=0.037). Both groups showed significant nents in inpatients with moderate to severe reduction of fasting glucose after 6 weeks. Only the exercise group showed reductions in diastolic blood pressure (p=0.049) and STUDY DESIGN: Randomized pilot trial.
waist circumference (p<0.001), increased HDL-C (p=0.01) and improvement in all ENDPOINTS: Effect on depressive symp-
cardiorespiratory fitness parameters at toms, with response to the intervention defined as ≥50% reduction from baseline in the Montgomery–Åsberg Depression Rat- CONCLUSIONS: The addition of exercise
ing Scale (MADRS); improvements in MetS training to standard antidepressant treat- components (fasting blood glucose, diastolic ment improved depressive symptoms, blood pressure, waist circumference and MetS factors and cardiorespiratory fitness high-density lipoprotein cholesterol, HDL- in patients hospitalized with moderate to C); and improvement in exercise capacity, severe depression. Given the association of measured by peak oxygen uptake (VO2 depression with cardiometabolic disorders, peak), ventilator anaerobic threshold (VAT) the authors recommend that depressed and workload expressed as Watts (W). patients receive adjunctive exercise training. METHOD: A total of 42 inpatients with
moderate to severe depression were
IN PATIENTS WITH BIPOLAR DISORDER:
COMPARISON WITH MAJOR DEPRESSIVE DISORDER
AND NON-PSYCHIATRIC CONTROLS
Journal of Psychosomatic Research, 2015 April; 78(4):391–8 AUTHORS: Silarova B, Giltay EJ, Van Reedt Dortland A, Van Rossum EF, Hoencamp E, Penninx BW, Spijker ATCENTRE FOR CORRESPONDENCE: PsyQ, Department of Mood Disorders, Rotterdam, the Netherlands BACkGROUND & AIM: Patients with
smoking status and severity of depressive bipolar disorder (BD) are at high risk for symptoms. In BD individuals, the adjust- metabolic syndrome (MetS), and the co- ment also included use of psychotropic occurrence of MetS and BD is associated with a more severe clinical presentation of BD, suicidality and decreased functional RESULTS: The prevalence of MetS was
recovery. Many of the studies investigating 28.4% among individuals with BD, 20.2% the prevalence of MetS in BD have used among those with MDD and 16.5% among either non-psychiatric controls or subjects non-psychiatric controls (p<0.001). The with schizophrenia as comparison groups. increased prevalence of MetS among BD The aim of this study was to investigate patients remained significant after adjust- the prevalence of MetS and its individual ment for sociodemographic and lifestyle components in patients with BD compared variables (odds ratio versus the MDD to those with major depressive disorder group: 1.52, 95% confidence interval (MDD) and a non-psychiatric control 1.09–2.12, p=0.02; OR versus controls: 1.79, 95% CI 1.20–2.67, p=0.005). Com-pared with non-psychiatric controls, BD STUDY DESIGN: Cohort study.
patients had higher mean waist circumfer-ence (88.8 cm versus 91.0 cm, respectively, ENDPOINTS: Prevalence of MetS and its
p=0.03) and lower mean systolic blood pressure (135.6 mmHg versus 132.7 mmHg, respectively, p=0.03). In logistic METHOD: The analysis included 241
regression analyses, the difference in MetS individuals with BD, 1648 with MDD and prevalence between the BD and MDD 542 non-psychiatric controls. Participants groups was more pronounced for patients were recruited from two longitudinal cohort with depressive symptoms than nonsympto- studies in the Netherlands: the Bipolar matic patients (adjusted OR 1.71, 95% CI Stress Study and the Netherlands Study of 1.12–2.61, p=0.01; and OR 1.03, 95% CI Depression and Anxiety. Diagnosis of MetS 0.56–1.90, p=0.92, respectively).
was established according to the National Cholesterol Education Program's Adult CONCLUSIONS: Patients with BD had a
Treatment Panel III criteria. The number of higher prevalence of MetS than patients MetS components was used as an indicator with MDD or non-psychiatric controls. of the severity of metabolic abnormali- Abdominal obesity and symptomatic ties. Multivariable analyses were adjusted depression were strongly associated with for age, sex, ethnicity, level of education, this increased risk.
CLINICAL EFFECTIVENESS OF COGNITIVE THERAPY
v. INTERPERSONAL PSYCHOTHERAPY
RESULTS OF A RANDOMIZED CONTROLLED TRIAL
Psychological Medicine, 2015 July; 45(10):2095–110 AUTHORS: Lemmens LH, Arntz A, Peeters F, Hollon SD, Roefs A, Huibers MJCENTRE FOR CORRESPONDENCE: Department of Clinical Psychological Science, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands BACkGROUND & AIM: Cognitive therapy
STUDY DESIGN: Single centre, parallel
(CT) and interpersonal psychotherapy (IPT) group, randomized controlled study.
are both effective treatments for major depressive disorder (MDD). Whether either ENDPOINT: Change from baseline in
therapy is superior to the other in terms depression severity, assessed during the of effects on disorder severity and course treatment phase (month 0–7) and monthly remains unclear. The aim of this study was to during 5 months of follow-up (month compare the clinical effectiveness of CT and IPT in a large cohort of depressed patients treated in an outpatient mental health clinic. METHOD: Adult patients with depression
The study also evaluated whether active were randomized to CT (n=76), IPT (n=75), treatment was superior to no treatment.
or a 2-month waiting list (WLC) control condition followed by treatment of choice (n=31). Patients allocated to CT or IPT Course of depression over time with CT, IPT or no treatment
received at least 12 sessions out of 16–20 planned individual sessions lasting 45 min- utes. Depression severity was assessed using the Beck Depression Inventory–II (BDI-II). RESULTS:
Both CT and IPT were associ- ated with considerable improvement in depression severity up to 12 months from baseline, exceeding change in the WLC con-dition. There were no significant differences in effects between CT and IPT. The results were not influenced by individual differen- Depression severity (BDI-II) 10 ces in therapists, baseline depression sever-ity, or total number of sessions. CONCLUSIONS: In patients with depres-
sion, both CT and IPT were equally effective in relieving depressive symptoms during treatment and this effect was sustained for a further 5 months of follow-up. Both inter- CT = cognitive therapy; IPT = interpersonal psychotherapy; WLC = waiting-list control; ventions were superior to no treatment.
BDI-II = Beck Depression Inventory. Values are mixed regression-based estimated means and95% confidence intervals corrected for baseline severity and quality-of-life utility score. AND PSYCHOMOTOR FUNCTION
IN DEPRESSED PATIENTS
TREATED WITH AGOMELATINE OR VENLAFAXINE
Pharmacopsychiatry, 2015 March; 48(2):65–71 AUTHORS: Brunnauer A, Buschert V, Fric M, Distler G, Sander K, Segmiller F, Zwanzger P, Laux GCENTRES: kbo-Inn-Salzach-Klinikum, Psychiatric Hospital, Wasserburg/Inn; Department of Psychiatry and Psychotherapy, Ludwig-Maximilians University Munich, Munich; and Institute for Psychological Medicine (IPM), Haag i. OB, Germany BACkGROUND & AIM: Antidepressant
50-minute on-road driving test conducted prescription and use are currently growing, by a licensed driving instructor blinded to particularly in the elderly, and there are treatment, diagnosis and test results. To concerns about the safety of drivers using control for retest effects, 20 healthy subjects psychopharmacological treatment. How- underwent the same testing schedule.
ever, only a few epidemiological studies investigating the effects of antidepressants RESULTS: After 4 weeks of treatment,
on road safety have been conducted, and depressive symptoms significantly improved experimental data on the driving behav- in the patients receiving agomelatine or ven- iour of antidepressant-treated patients are lafaxine. There was a significant improve- sparse. The aim of this study was to assess ment in global driving ability score after 14 the effects of the newer antidepressants days of treatment in both the agomelatine agomelatine and venlafaxine on psycho- group (z= –2.16, p<0.05) and the venlafax- motor functions related to driving skills and ine group (z= –2.74, p<0.01), which was on driving performance in patients with sustained at day 28. After controlling for major depression.
retest effects, both patient groups had sig-nificantly improved scores in their reactivity STUDY DESIGN: Randomized case–control
and stress-tolerance tests, and a significant improvement in concentration was observed in the agomelatine group. In the on-road ENDPOINTS: Global driving ability score
test, 72.5% of patients were rated as good and on-road test results.
drivers and 22.5% as satisfactory drivers. There were no significant differences METHOD: The study included 40 inpa-
between the treatment groups in either the tients with major depression (Hamilton psychomotor or on-road tests, but neither Rating Scale for Depression score ≥20) who patient group reached the same level of per- were randomized 1:1 to receive agomelatine formance as the healthy controls.
or venlafaxine at a dose selected on an indi-vidual basis by the treating psychiatrist. All CONCLUSION: Treatment with agomela-
patients underwent psychomotor and visual tine or venlafaxine resulted in significantly perception tests prior to treatment and at improved performance in tasks related 14 days and 28 days after treatment to to driving ability in patients with major assess visual perception, selective attention, depression, with the majority being rated vigilance, reactivity and stress tolerance as fit to drive in an on-road driving test 28 (global driving ability score). On day 28, days after treatment initiation.
participants also underwent a standardized INSOMNIA AND SOMNOLENCE
ASSOCIATED WITH SECOND-GENERATION
ANTIDEPRESSANTS DURING THE TREATMENT
OF MAJOR DEPRESSION:
Journal of Clinical Psychopharmacology, 2015 June; 35(3):296–303 AUTHORS: Alberti S, Chiesa A, Andrisano C, Serretti ACENTRES: Department of Biomedical and Neuromotor Science, University of Bologna, Bologna; and Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Messina, Italy BACkGROUND & AIM: Second-generation
were uncontrolled trials. Pooled odds ratios antidepressant drugs, such as selective sero - (ORs) for insomnia and somnolence rates tonin reuptake inhibitors (SSRI) and sero- were calculated using a random effects tonin–norepinephrine reuptake inhibitors model, and heterogeneity was assessed.
(SNRI), are frequently associated with insomnia or daytime somnolence, which RESULTS: Ten of the 14 antidepressants
can be beneficial or harmful to the patient were associated with significantly higher depending on their symptom profile. How- rates of short-term insomnia compared with ever, the rates of insomnia and daytime placebo, with bupropion and desvenlafax- somnolence have not been compared among ine having the highest incidence rates. The the individual antidepressants. The aim only antidepressant with a lower likelihood of this meta-analysis was to compare the of inducing insomnia compared with pla- short-term rates of insomnia and somno- cebo was agomelatine. Eleven of the antide- lence associated with 14 second-generation pressants were associated with significantly antidepressants during treatment of major higher rates of short-term somnolence compared with placebo, with fluvoxamine and mirtazapine demonstrating the highest STUDY DESIGN: Meta-analysis.
frequency of somnolence. Bupropion was the only antidepressant with a significantly ENDPOINTS: Short-term insomnia and
lower risk of inducing somnolence than somnolence rates.
placebo. Sensitivity analyses of only the ran-domized, double-blind, placebo-controlled METHOD: A systematic search of the
trials confirmed the overall results, with Medline, ISI Web of Science and Cochrane only a small degree of variation.
databases was performed to identify con-trolled and uncontrolled studies published CONCLUSION: Second-generation antide-
up to January 2013 that provided data on pressants vary in terms of their association short-term (up to 12 weeks) drug-related with insomnia or somnolence, most likely insomnia and/or somnolence rates in adult due to their different modes of action, but patients with major depression treated most are associated with a higher risk of with a second-generation antidepressant. insomnia and somnolence than placebo. A minimum study duration of 6 weeks Understanding the differences among anti- was required. A total of 276 trials were depressant drugs in terms of their effects on included in the meta-analysis, of which sleepiness could be useful for tailoring the 223 were randomized controlled, seven choice of medication to the specific needs of were non-randomized controlled and 46 the individual patient.
SCREEN TIME IS ASSOCIATED WITH DEPRESSION
AND ANXIETY IN CANADIAN YOUTH
Preventive Medicine, 2015 April; 73:133–8 AUTHORS: Maras D, Flament MF, Murray M, Buchholz A, Henderson KA, Obeid N, Goldfield GSCENTRES: Carleton University Department of Psychology; University of Ottawa Institute of Mental Health Research, Royal Ottawa Mental Health Centre; University of Ottawa Department of Psychology; Centre for Healthy Active Living, Children's Hospital of Eastern Ontario; Eating Disorder Program, Children's Hospital of Eastern Ontario; and Healthy Active Living & Obesity Research Group, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Canada BACkGROUND & AIM: The use of
Adolescent Lifestyles (REAL) study between screen-based electronic devices (such as 2006 and 2010. Mental health status television, video games and computers) is was assessed using the Children's Depres- popular among young people in industrial- sion Inventory and the Multidimensional ized societies and is associated with obesity, Anxiety Scale for Children–10. Screen cardiometabolic risk factors and diabetes. time (hours/day of television, video games Although depression and anxiety are com- and computer use) was assessed using the mon among adolescents, little research Leisure-Time Sedentary Activities question- has been conducted into the relationship naire. Associations between screen time and between sedentary, screen-based activi- symptoms of depression and anxiety were ties and mental health in this age group. identified using multiple linear regression The evidence to date is contradictory, with some studies showing a positive association between screen time and anxiety or depres- RESULTS: Duration of screen time was
sion and others finding no such association. associated with the severity of both The aim of this study was to examine the depression (β=0.23, p<0.001) and anxi- relationships between sedentary screen time ety (β=0.07, p<0.004) after controlling and symptoms of depression and anxiety for age, sex, ethnicity, parental education, in a large community sample of Canadian geographic area, physical activity and body mass index. Time spent playing video games (β=0.13, p<0.001) and using the computer STUDY DESIGN: Cohort study.
(β=0.17, p<0.001), but not watching tele-vision, were associated with more severe ENDPOINTS: Screen time and any asso-
depressive symptoms. Video game playing ciation with symptoms of depression and (β=0.11, p<0.001) was also predictive of more severe anxiety symptoms.
METHOD: Cross-sectional data were col-
CONCLUSION: Longer duration of screen
lected from 2482 English-speaking grade time was associated with more severe 7–12 Canadian students (1048 male) par- symptoms of depression and anxiety in ticipating in the Research on Eating and PREDICTING THE NATURALISTIC COURSE
OF MAJOR DEPRESSIVE DISORDER
USING CLINICAL AND MULTIMODAL
A MULTIVARIATE PATTERN RECOGNITION STUDY
Biological Psychiatry, 2014 November 29; Epub ahead of print AUTHORS: Schmaal L, Marquand AF, Rhebergen D, van Tol MJ, Ruhé HG, van der Wee NJ, Veltman DJ, Penninx BWCENTRE FOR CORRESPONDENCE: Department of Psychiatry and Neuroscience Campus Amsterdam, VU University Medical Center Amsterdam, Amsterdam, the Netherlands BACkGROUND & AIM: The early identi-
(n=59). The prognostic value of neuroimag- fication of patients with major depressive ing data and clinical characteristics (includ- disorder (MDD) who are at risk of expe- ing baseline MDD severity, MDD duration riencing a chronic disease course would and comorbidity) for discriminating among enable appropriate treatment strategies to these trajectories was evaluated using a be implemented promptly. Although some multivariate pattern recognition method clinical characteristics are known to be involving Gaussian process classifiers.
linked with chronic MDD, neurobiological markers are lacking. There is some evidence RESULTS: Functional MRI measures of the
that neuroimaging findings could be help- neural responses to emotional faces could ful, but their relevance for predicting risk be used to discriminate between patients at the level of the individual patient has not with a chronic course and those with fast been demonstrated. This study evaluated remission (based on responses to angry and the prognostic value of different neuroimag- happy faces; accuracy 73%), and between ing modalities, clinical characteristics, and those with a chronic course and those with their combination, for classifying MDD a gradually improving course (based on course trajectories in a naturalistic cohort of happy and neutral faces; accuracy 69%). patients with MDD.
MDD course trajectories could not be dis-criminated using structural MRI or func- STUDY DESIGN: Cohort study.
tional MRI related to executive functioning. Clinical characteristics could be used to ENDPOINTS: Prediction of MDD course
discriminate patients with a chronic course from those with remission (accuracy 69%), but this became non-significant when age METHOD: The study included 118 patients
differences were accounted for. Combining with MDD who underwent structural and different neuroimaging modalities and clini- functional magnetic resonance imaging cal characteristics did not increase the accu- (MRI), including assessments of brain acti- racy for predicting course trajectories.
vation during emotional facial processing and during executive functioning. Patients CONCLUSION: Neuroimaging data on
were followed up clinically for 2 years using responses to emotional facial expressions the Life Chart Interview to measure symp- were useful for predicting the course of toms each month, and a latent class growth MDD, and such predictions were more analysis of these data identified three accurate than those based on clinical data MDD trajectories: chronic (n=23), grad- ual improving (n=36) and fast remission ANTIDEPRESSANT DRUG DEVELOPMENT:
FOCUS ON TRIPLE MONOAMINE REUPTAkE INHIBITION
Journal of Psychopharmacology, 2015 May; 29(5):526–44 AUTHOR: Lane RMCENTRE: Isis Pharmaceuticals, Carlsbad, California, USA BACkGROUND & AIM: New antidepres-
dopamine reuptake inhibition to counteract sant drugs are needed to treat major depres- hypodopaminergic effects. sive disorder (MDD), as many patients Trials of TRIs have so far been unsuc- only partially respond or have no clinically cessful, with results indicating a lack of meaningful response to current treatments. efficacy compared with placebo or standard However, industry investment in antide- care in phase 2 clinical studies. However, pressant drug development has waned for these findings do not negate the hypothesis various reasons, including the high rate of that a TRI could be effective in a subgroup failure of antidepressants in late-stage clini- of MDD patients, as TRI development pro- cal trials. Triple-reuptake inhibitors (TRIs) grammes have made assumptions concern- that simultaneously inhibit serotonin, nor- ing suitable target populations and have epinephrine and dopamine reuptake would lacked translational research studies with potentially have greater efficacy than cur- pharmacodynamic biomarkers and predic- rently available drugs in some patients with tive animal models. Also, the optimal mix MDD. The author summarized the evidence of relative inhibitory potencies for the three for TRIs and discussed issues around their transporters is still unknown.
Addressing these limitations in future drug development would allow a TRI to ARTICLE TYPE: Review.
be compared more accurately with placebo and existing antidepressants in the target FINDINGS: Patients with MDD form a
population. They would also allow dose– heterogeneous group with a wide range response relationships to be established of overlapping symptoms. The successful for efficacy and safety, and would indicate development of next-generation antidepres- whether cardiovascular effects are manage- sants will require a deeper understanding able in the proposed dose range.
of individual differences in biology and treatment response, as well as the ability to CONCLUSIONS: Cost-effective and suc-
translate this knowledge into the develop- cessful drug development of TRIs should be ment of drugs targeting specific subgroups possible with the use of relevant biomarkers, of patients who share the same symptoms. improved animal models and identification of Patients unresponsive to current treatment the specific target population. Success would who have a high burden of decreased posi- induce renewed investment by the pharma- tive mood symptoms and comorbidities that ceutical industry in the development of novel suggest reward-network dysfunction could antidepressant medications and improve the potentially benefit from the addition of therapeutic outlook for patients with MDD.
A LIFETIME APPROACH
TO MAJOR DEPRESSIVE DISORDER:
THE CONTRIBUTIONS OF PSYCHOLOGICAL INTERVENTIONS
IN PREVENTING RELAPSE AND RECURRENCE
Clinical Psychology Review, 2015 February 26; Epub ahead of print AUTHORS: Bockting CL, Hollon SD, Jarrett RB, Kuyken W, Dobson KCENTRE: Department of Clinical Psychology, University of Groningen, Groningen; and Department of Clinical and Health Psychology, Utrecht University, Utrecht, the Netherlands; Department of Psychology, Vanderbilt University, Nashville, Tennessee; and The University of Texas Southwestern Medical Center, Dallas, Texas, USA; Department of Psychiatry, University of Oxford, Oxford, UK; Department of Psychology, University of Calgary, Alberta, Canada BACkGROUND & AIM: Major depressive
cognitive-behavioural therapy after disorder (MDD) often follows a recurrent response/remission has been achieved (con- course. Strategies for preventing relapse tinuation treatment) and after the patient and recurrence include the continuation has recovered fully from the index episode of antidepressant medication and the use (maintenance treatment) has been shown of psychological interventions. This article to further reduce the risk of relapse or considers the role of psychological interven- recurrence. There is some evidence that tions in the prevention of relapse and recur- continuation/maintenance therapy with rence of MDD, based on a review of the interpersonal psychotherapy may also be Interventions started after remission:
TYPE OF ARTICLE: Review.
Well-being cognitive therapy, mindfulness-based cognitive therapy and preventive FINDINGS: The mechanisms underlying
cognitive therapy started in patients who the effectiveness of preventive psychological are currently in remission but who are at interventions are not fully understood, but high risk of recurrence can be effective in probably involve changes in dysfunctional reducing the risk of relapse or recurrence. beliefs or the process of cognition. Preven- Behavioural activation also shows promise, tive psychological therapies may be started based on a single study.
during the acute phase of the illness, may be Subgroups who benefit the most: Cogni-
continued in patients who have responded tive therapy continuation and preventive to acute-phase treatment, or may be started interventions started after remission appear when patients are in remission. to provide the greatest differential benefit Acute-phase interventions: Cognitive
for those patients who are at greatest risk of behavioural therapy administered during relapse/recurrence, including patients with the acute phase of illness reduces the risk unstable remission, a higher number of pre- of relapse for a period that extends beyond vious episodes, early age of onset, and more the end of treatment. There is also some severe childhood trauma.
evidence that it may reduce the risk of CONCLUSION: Psychological interventions
can reduce the risk of relapse or recurrence ventions: Continuing treatment with
in patients with MDD.
CAN ATYPICAL ANTIPSYCHOTIC AUGMENTATION
REDUCE SUBSEQUENT TREATMENT FAILURE
MORE EFFECTIVELY AMONG DEPRESSED PATIENTS
WITH A HIGHER DEGREE
OF TREATMENT RESISTANCE?
A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
International Journal of Neuropsychopharmacology, 2015 March 13; Epub ahead of print AUTHORS: Wang HR, Woo YS, Ahn HS, Ahn IM, Kim HJ, Bahk WMCENTRES: Department of Psychiatry, College of Medicine, The Catholic University of Korea; and Department of Preventive Medicine, College of Medicine, Korea University, Seoul, Korea; Department of Literary Arts, Brown University, Rhode Island, USA BACkGROUND & AIM: Augmentation
from meta-analysis of response rates treatment with atypical antipsychotic agents because only one of them produced suitable has been shown to be an effective option for patients with major depressive disorder (MDD) that is resistant to standard antide- RESULTS: Based on the pooled data for
pressant therapy. However, it is not known treatment-resistant depression, atypical whether the degree of treatment resistance antipsychotic augmentation of antidepres- present has an impact on the effect of such sant therapy was more efficacious than augmentation therapy. The aim of this antidepressant monotherapy in treatment- meta-analysis was to determine whether resistant depression in terms of the response the effect size of atypical antipsychotic aug- rate (risk ratio 1.38, 95% confidence inter- mentation in MDD varies according to the val 1.25–1.53) and the remission rate (RR degree of treatment resistance.
1.62, 95% CI 1.42–1.85). Effect sizes for the response rate increased with increasing STUDY DESIGN: Meta-analysis.
degree of treatment resistance, with risk ratios rising from 1.24 for the TRD1 sub- ENDPOINTS: Response and remission
group to 1.58 for the TRD2–4 subgroup (z=0.121257, p=0.05). Effect sizes for the remission rate did not differ significantly METHOD: A search of the Cochrane
according to the degree of treatment resist- Library, Embase, Medline and KoreaMed ance. Based on the pooled data for non- databases for randomized, double-blind, resistant depression, atypical antipsychotic placebo-controlled, acute-phase trials augmentation was not superior to antide- evaluating the efficacy of atypical anti- pressant monotherapy in terms of remission psychotic augmentation in patients with rates (RR 0.89, 95% CI 0.69–1.14).
non-psychotic MDD identified 11 trials (n=3341), including 9 in treatment-resistant CONCLUSIONS: Augmentation therapy
depression and 2 in non-resistant depres- with atypical antipsychotics was superior sion. The degree of treatment resistance to antidepressant monotherapy in patients was classified according to the number of with treatment-resistant MDD, and had failed treatment trials during the index epi- a greater effect in patients with a higher sode: one (TRD1), two (TRD2), or two to degree of treatment resistance. Atypical four (TRD2–4). Results were pooled using antipsychotic augmentation therapy was a random-effects meta-analysis. The trials not superior to antidepressant monotherapy in non-resistant depression were excluded in patients with non-resistant MDD.
framingham on depression
is supported by an unrestricted
educational grant from
SERVIER Deutschland GmbH
München, Germany

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