Marc Blom

Combination Treatment for Acute Depression Is Superior Only when Psychotherapy Is Added to Medication

Background: Although several forms of effective therapy exist for outpatients suffering from major depressive disorder, many patients do not profit from treatment. Combining psychotherapy and medication may be an effective strategy. However, earlier studies have rarely found a clear advantage for the combination. Where an advantage was found, a possible placebo effect of adding 2 types of treatment could not be ruled out as cause for the superior effect of the combination. Methods: A total of 353 patients were screened, of whom 193 were randomized over 4 conditions: nefazodone plus clinical management, interpersonal psychotherapy (IPT), the combination of the two or the combination of IPT and pill-placebo. All patients suffered from major depressive disorder and had a score of at least 14 on the 17-item Hamilton Rating Scale (HAMD). The patients were treated for 12–16 weeks. At baseline, at 6 weeks and on completion of treatment, ratings were performed by independent raters. The primary outcome measure was the HAMD, and the Montgomery-Asberg Depression Rating Scale (MADRS) the secondary outcome measure. Results: Of the 193 patients included, 138 completed the trial. All treatments were effective. Using a random regression model, no differences between treatments were found on the HAMD. On the MADRS, however, the combination of medication with psychotherapy was more effective in reducing depressive symptoms compared to medication alone, but not to psychotherapy alone or IPT with pill-placebo. Conclusions: The results of this study yield support for the use of combining medication with psychotherapy instead of using medication only in the treatment of depressed outpatients. Combination treatment does not have an advantage over psychotherapy alone in the present study.

Preventing relapse in recurrent depression using mindfulness-based cognitive therapy, antidepressant medication or the combination: trial design and protocol of the MOMENT study

BackgroundDepression is a common psychiatric disorder characterized by a high rate of relapse and recurrence. The most commonly used strategy to prevent relapse/recurrence is maintenance treatment with antidepressant medication (mADM). Recently, it has been shown that Mindfulness-Based Cognitive Therapy (MBCT) is at least as effective as mADM in reducing the relapse/recurrence risk. However, it is not yet known whether combination treatment of MBCT and mADM is more effective than either of these treatments alone. Given the fact that most patients have a preference for either mADM or for MBCT, the aim of the present study is to answer the following questions. First, what is the effectiveness of MBCT in addition to mADM? Second, how large is the risk of relapse/recurrence in patients withdrawing from mADM after participating in MBCT, compared to those who continue to use mADM after MBCT?Methods/designTwo parallel-group, multi-center randomized controlled trials are conducted. Adult patients with a history of depression (3 or more episodes), currently either in full or partial remission and currently treated with mADM (6 months or longer) are recruited. In the first trial, we compare mADM on its own with mADM plus MBCT. In the second trial, we compare MBCT on its own, including tapering of mADM, with mADM plus MBCT. Follow-up assessments are administered at 3-month intervals for 15 months. Primary outcome is relapse/recurrence. Secondary outcomes are time to, duration and severity of relapse/recurrence, quality of life, personality, several process variables, and incremental cost-effectiveness ratio.DiscussionTaking into account patient preferences, this study will provide information about a) the clinical and cost-effectiveness of mADM only compared with mADM plus MBCT, in patients with a preference for mADM, and b) the clinical and cost-effectiveness of withdrawing from mADM after MBCT, compared with mADM plus MBCT, in patients with a preference for MBCT.Trial registrationClinicalTrials.gov: NCT00928980

The Effectiveness of the Cognitive Behavioral Analysis System of Psychotherapy for Chronic Depression : A Randomized Controlled Trial

Background: It is widely agreed that chronic depression is difficult to treat, knowledge about optimal treatment approaches is emerging. Method: A multisite randomized controlled trial was conducted comparing the cognitive behavioral analysis system of psychotherapy (CBASP), a psychotherapy model developed specifically to treat chronic depression (n = 67) with care as usual (CAU; evidence-based treatments, n = 72) over a period of 52 weeks, with 23 sessions on average, in 3 outpatient clinics in the Netherlands. In both arms algorithm-based pharmacotherapy was provided. Patients (aged 18-65) met criteria for a DSM-IV diagnosis of major depressive disorder with diagnostic specifiers (chronic, without interepisode recovery) or with co-occurring dysthymic disorder indicating a chronic course. The Inventory for Depressive Symptomatology (IDS) Self-Report was used as the primary outcome measure. Mixed-effects linear regression analysis was used to compare the changes on the IDS scores between CBASP and CAU. The IDS was administered before treatment, and after 8, 16, 32 and 52 weeks. Results: At week 52, patients assigned to CBASP had a greater reduction of depressive symptoms compared to patients assigned to CAU (t = -2.00, p = 0.05). However, CBASP and CAU did not differ from each other on the IDS after 8 weeks (t = 0.49, p = 0.63), 16 weeks (t = -0.03, p = 0.98) and 32 weeks (t = -0.17, p = 0.86) of treatment. Conclusions: This trial shows that CBASP is at least as effective as standard evidence-based treatments for chronic depression. In the long run, CBASP appears to have an added effect.

Functional polymorphism of the glucocorticoid receptor gene associates with mania and hypomania in bipolar disorder

OBJECTIVES In affective disorders, dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis is a frequently observed phenomenon. Subtle changes in glucocorticoid receptor (GR) functioning caused by polymorphisms of the GR gene (NR3C1) may be at the base of the altered reaction of the HPA axis to stress and subsequently related to the development and course of affective disorders. The aim of our study is to evaluate associations between GR gene polymorphisms and bipolar disorder (BD). METHODS In this study, 245 patients with BD were interviewed to confirm diagnosis and BD subtype. Data on medication use and sociodemographic details were also collected. The control group consisted of 532 healthy blood donors, from which data on sex and age were collected. To perform genotyping, blood was collected from all patients and healthy controls. RESULTS A trend was found for a protective effect of the exon 9beta polymorphism (p = 0.14) and the TthIIII polymorphism (p < 0.05) on the manifestation of the disease. These effects were significantly influenced by male gender for both polymorphisms. Patients with BD and the A/G variant in exon 9beta had significantly fewer manic and hypomanic episodes than noncarriers (p < 0.05). No further associations were found with the other investigated GR gene polymorphisms and BD. These findings were not corrected for multiple comparisons. CONCLUSIONS We conclude that the exon 9beta polymorphism and the TthIIII polymorphism of the GR gene may be associated with a protective effect on the clinical manifestation and course in patients with BD. Furthermore, no associations were found between the other studied GR gene polymorphisms and this disease.

Discontinuation of antidepressant medication after mindfulness-based cognitive therapy for recurrent depression: randomised controlled non-inferiority trial

Background Mindfulness-based cognitive therapy (MBCT) and maintenance antidepressant medication (mADM) both reduce the risk of relapse in recurrent depression, but their combination has not been studied. Aims To investigate whether MBCT with discontinuation of mADM is non-inferior to MBCT+mADM. Method A multicentre randomised controlled non-inferiority trial (ClinicalTrials.gov: NCT00928980). Adults with recurrent depression in remission, using mADM for 6 months or longer (n = 249), were randomly allocated to either discontinue (n = 128) or continue (n = 121) mADM after MBCT. The primary outcome was depressive relapse/recurrence within 15 months. A confidence interval approach with a margin of 25% was used to test non-inferiority. Key secondary outcomes were time to relapse/recurrence and depression severity. Results The difference in relapse/recurrence rates exceeded the non-inferiority margin and time to relapse/recurrence was significantly shorter after discontinuation of mADM. There were only minor differences in depression severity. Conclusions Our findings suggest an increased risk of relapse/recurrence in patients withdrawing from mADM after MBCT.

Adding mindfulness-based cognitive therapy to maintenance antidepressant medication for prevention of relapse/recurrence in major depressive disorder: Randomised controlled trial.

BACKGROUND Mindfulness-based cognitive therapy (MBCT) and maintenance antidepressant medication (mADM) both reduce the risk of relapse in recurrent depression, but their combination has not been studied. Our aim was to investigate whether the addition of MBCT to mADM is a more effective prevention strategy than mADM alone. METHODS This study is one of two multicenter randomised trials comparing the combination of MBCT and mADM to either intervention on its own. In the current trial, recurrently depressed patients in remission who had been using mADM for 6 months or longer (n=68), were randomly allocated to either MBCT+mADM (n=33) or mADM alone (n=35). Primary outcome was depressive relapse/recurrence within 15 months. Key secondary outcomes were time to relapse/recurrence and depression severity. Analyses were based on intention-to-treat. RESULTS There were no significant differences between the groups on any of the outcome measures. LIMITATIONS The current study included patients who had recovered from depression with mADM and who preferred the certainty of continuing medication to the possibility of participating in MBCT. Lower expectations of mindfulness in the current trial, compared with the parallel trial, may have caused selection bias. In addition, recruitment was hampered by the increasing availability of MBCT in the Netherlands, and even about a quarter of participants included in the trial who were allocated to the control group chose to get MBCT elsewhere. CONCLUSIONS For this selection of recurrently depressed patients in remission and using mADM for 6 months or longer, MBCT did not further reduce their risk for relapse/recurrence or their (residual) depressive symptoms.

Interpersonal and Social Rhythm Group Therapy for Patients with Bipolar Disorder

This article describes Interpersonal and Social Rhythm Therapy (IPSRT) adapted for use in a group setting for patients with bipolar disorder. In a preliminary efficacy study, we studied the pre-post group treatment effect on affective symptoms. One-year pre-post findings in the IPSRT group indicated that this modality was effective in reducing depressive symptoms and might reduce the number of hospital admissions. Also, group IPSRT increased stability of the social rhythm, which is thought to be important in reducing recurrence of manic and depressive episodes. These findings suggest that group IPSRT could be an additional treatment option for patients with bipolar disorder who continue to have mood episodes despite adequate pharmacotherapy and psychoeducation.

Treatment of Depression in Patients from Ethnic Minority Groups in the Netherlands

This article presents the results of a large efficacy study comparing different forms of therapy for major depressive disorder (MDD), including interpersonal psychotherapy (IPT) and pharmacotherapy. Patients were randomized to either IPT, IPT in combination with anti-depressant medication, IPT in combination with pill-placebo or medication only. The primary outcome measure was the Hamilton Rating Scale for Depression (HAMD). Patients were treated for 12 to 16 weeks. Ratings were performed at baseline, after 6 weeks of treatment and at the end of treatment. Ethnic minority patients (EMP) had higher scores on the HAMD than non-EMP for every rating period. However, the rate of improvement was the same for EMP and non-EMP. The higher mean scores of EMP on the HAMD could not be explained as solely due to higher scores on somatic items of the rating scales. The attrition rate in EMP (45.9%) was significantly higher than in non-EMP (24.4%), even in the structured treatment format studied. The results suggest that standard antidepressant therapy, be it medication, psychotherapy or both, may be effective for depressed minority patients but therapists should focus on enhancing adherence to treatment.

Werkzaamheid van interpersoonlijke psychotherapie

Vanaf het ontstaan van IPT in de jaren zeventig van de vorige eeuw is IPT nauw verbonden geweest met wetenschappelijk onderzoek. Vooral Gerald Klerman stimuleerde onderzoek naar deze nieuwe vorm van psychotherapie, bijna alsof het een nieuw medicijn was. Hij wilde dat de effectiviteit wetenschappelijk aangetoond werd. Er kan niet genoeg benadrukt worden hoezeer dat een breuk was binnen de psychotherapeutische wereld. Tot in de jaren zeventig waren veruit de meeste therapeuten (in de VS, maar in Europa was de situatie niet anders) ervan overtuigd dat gerandomiseerd onderzoek, de gouden standaard in effectonderzoek, mogelijk noch wenselijk was (Lambert & Ogles, 2004).

Toekomst van IPT

Interpersoonlijke psychotherapie wordt inmiddels door duizenden therapeuten in tientallen landen uitgevoerd. Er is veel onderzoek dat inmiddels overtuigend aantoont dat IPT effectief is in de behandeling van depressie en enkele andere psychische stoornissen. Oorspronkelijk ontwikkeld in de jaren zeventig van de vorige eeuw, zijn het format en het protocol van IPT in al die jaren niet veranderd. Dit is prettig als men een meta-analyse wil verrichten (Cuijpers e.a., 2011), maar het is de vraag of er toch geen aanpassingen binnen het model nodig zijn. In dit hoofdstuk zullen we een aantal onderwerpen bespreken waarvan we denken dat zij voor de toekomst van IPT en van psychotherapie in het algemeen, belangrijk zijn.