A systematic review and meta-analysis of cognitive behavioral and psychodynamic therapy for depression in Parkinson s disease patients

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1 DOI /s REVIEW ARTICLE A systematic review and meta-analysis of cognitive behavioral and psychodynamic therapy for depression in Parkinson s disease patients Cheng-Long Xie Xiao-Dan Wang Jie Chen Hua-Zhen Lin Yi-He Chen Jia-Lin Pan Wen-Wen Wang Received: 8 October 2014 / Accepted: 18 February 2015 Ó Springer-Verlag Italia 2015 Abstract Numerous practice guidelines have recommended cognitive behavioral therapy (CBT) and psychodynamic therapy as a treatment of choice for depression in Parkinson s disease (PD). However, no recent meta-analysis has examined the effects of brief psychotherapy (which includes both CBT and psychodynamic therapy) for adult depression in PD. We decided to conduct such a systematic review and meta-analysis. We included randomized controlled trials (RCTs) examining the effects of brief psychotherapy compared with control groups, other support nursing, or pharmacotherapy. The quality of included studies was strictly evaluated. Twelve studies including 766 patients met all inclusion criteria. The result showed that brief psychotherapy could evidently improve the HAMD (p \ ) and Moca scale (p = 0.006). C. Xie and X.-D. Wang contributed equally to this work. C.-L. Xie J. Chen H.-Z. Lin W.-W. Wang (&) The Center of Traditional Chinese Medicine, The Second Affiliated Hospital and Yuying Children s Hospital of Wenzhou Medical University, Wenzhou , www @163.com C.-L. Xie Department of Neurology, Xinhua Hospital Affiliated to the Medical School of Shanghai Jiaotong University, 1665 Kongjiang Road, Shanghai , X.-D. Wang Department of Neurology, Ruijin Hospital North Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai , Y.-H. Chen J.-L. Pan The Center of Cardiology, The Second Affiliated Hospital and Yuying Children s Hospital of Wenzhou Medical University, Wenzhou , There was no statistical significance in PDQ-39 scale (p = 0.31). In the subgroup analysis by types of brief psychotherapy, the efficacy of psychodynamic psychotherapy was better than CBT (SMD =-2.02 vs SMD =-0.90) for the outcome measure according to HAMD scale. Meanwhile, we found brief psychotherapy in was more effective than in US (SMD =-1.54 vs SMD =-1.23), and in low quality studies was more efficacious than in high quality studies (SMD =-1.50 vs SMD =-1.33). Time of brief psychotherapy treatment above 6 weeks was superior to studies with less than 6 weeks treatment. We found brief psychotherapy is probable effective in the management of depression in PD patients. But one reason to undermine the validity of findings is high clinical heterogeneity and low methodological quality of the included trials. Keywords Cognitive behavioral therapy Psychosocial treatments Parkinson s disease Depression Systematic review Meta-analysis Introduction Although Parkinson s disease (PD) is diagnosed in the light of the classic features of progressive motor symptoms, it is now widely noted that non-motor symptoms (NMS) are common, and occur across all stages of the disease [1]. In clinical settings, about a quarter of patients with PD have a major depressive syndrome, and about half have clinically severe depressive symptoms [2]. They are associated with functional impairment, cognitive decline, and are the main determinant for poor health-related quality of life in patients with PD [3]. Research has also shown that depression is one of the greatest predictors of poor quality of life in PD

2 and consistently rated as go against healthy and functional ability [4]. Meanwhile, depressive disorders in PD patients also result in increased health care costs in the population, raising both direct and indirect costs. Consequently, understanding depression and reasonable management in patients with PD is vital to achieve the optimal care that is needed for patients with this disease. To date, the underlying mechanisms of depression in PD patients are not known in detail, but changes in brain structure, signaling by neurotransmitters, levels of inflammatory and neurotrophic factors are all suggested to contribute to its development. Meanwhile, psychological factors and pain could also have roles in depression [5]. Therefore, depression in PD is generally considered due both to neurobiological vulnerability and to psychological factors. To our knowledge, the treatment of depression in PD (dpd) is significant because of its known association with worse severity and prognosis of the disease. There is no doubt that medication therapy continues to be the first line of treatment for dpd [6]. Among them, selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) are the two most commonly prescribed antidepressants in patients with PD [7]. Several placebo-controlled trials have demonstrated the benefits of such antidepressant use for PD patients [8]. However, a recent review of antidepressants on dpd found the effect of antidepressants to be small and statistically insignificant [9]. What is more, long-term use with SSRIs can lead to worsening of parkinsonian symptoms and TCA side effects such as sedation, orthostatic hypotension and anticholinergic effects can be problematic in patients with PD who have a higher rate of incidence of cognitive deficits [10]. Consequently, there has been an emerging interest in the utility of alternative and non-pharmacological treatments for depression in PD patients. Recent researches have focused on non-pharmacological approaches to treating depression in PD patients [11]. These therapy strategies serve as alternatives or adjuncts to medications and patients with PD report pleasure and positive opinions with respect to non-medication treatment options [12]. Among them, cognitive-behavior therapy (CBT) is a skilled-based approach that focuses on changing maladaptive behaviors, beliefs and patterns of thinking that negatively influence emotions [13]. In addition, other kinds of psychotherapy (psychodynamic psychotherapy) also have showed the promising future for dpd patients, which refer to a briefer form of therapy where the therapist is more active and focuses on a particular problem, rather than difficulties affecting the whole personality [14]. What is more, psychodynamic psychotherapy attempts to explore, through talking, play and the formation of a therapeutic relationship, how earlier experiences influence and perhaps seriously distort current thoughts, feelings, behaviors and relationships [15]. CBT and psychodynamic psychotherapy both belong to psychotherapy. Up to now, several case series and RCT studies have demonstrated the promise of using CBT and psychodynamic psychotherapy for dpd. Moreover, a randomized controlled trial (RCT) conducted by Dobkin et al. [16] found a CBT treatment package to be effective for dpd. An additional adaptation of CBT to be delivered via telephone was also found to be feasible and beneficial for dpd [17]. At present, CBT is an extensive researched treatment that has been found to be very good for treating depression in people without PD and has been successful in reducing symptoms of depression in people with diverse chronic medical and neurological conditions. However, there has been very little work applying the CBT and approach to dpd [18]. There is a need to examine research in related field to see whether the CBT treatment option for PD depression is likely to be effective. To our best knowledge, only a handful of RCT for depression in PD have been published, and they mainly focused on pharmacotherapy, despite the appearance decades ago of multicenter RCT for CBT or psychodynamic psychotherapy in people with major depression but not PD. Meanwhile, Armento et al. [19] reported a clinical review of CBT treatments for depression and anxiety symptoms in PD; which showed CBT was potentially a useful treatment for patients with PD and comorbid depression and/or anxiety, but more systematic research will be necessary to measure its effects. Troeung et al. [20] reported a meta-analysis that showed there remained a lack of controlled trials for both pharmacological and non-pharmacological treatments for depression and anxiety in PD which limited the conclusions. Non-pharmacological approaches show potential for depression in PD and more research is required. Consequently, the aim of this meta-analysis is to provide a systematic evaluation of the efficacy of brief psychotherapy (which including CBT and psychodynamic psychotherapy) treatments for depression in PD to better inform clinical care and future research. Methods Inclusion and exclusion criteria Only RCTs which evaluate brief psychotherapy for dpd patients were included in this review. Brief psychotherapy was predefined as a therapy in which the therapist concentrates on the impact that a patient s present dysfunctional thoughts affect present behavior and function, mainly including cognitive therapy, behavioral activation and psychodynamic psychotherapy. The treatment is aimed at evaluating, challenging and modifying the patient s

3 dysfunctional beliefs [21]. To prevent bias, inclusion criteria were pre-specified as the following: (a) published in a peer-reviewed journal; (b) conducted to evaluate the brief psychotherapy alone or combination other treatments compared with the effects of a control group (placebo) or another type of treatment (support treatment or pharmacotherapy). Support treatment encourages members to describe their feelings about having such disease. To identify shared problems, fears, concerns and hopes; to discuss how these conditions are handled and to adopt supportive and encouraging roles toward others in the group. There is considerable member-initiated discussion of how problems related to such disease were handled, and participants are encouraged to share with and learn from experiences raised by others in the same group. Skills training, cognitive therapy, behavior rehearsal, contracting, and practice assignments were not employed in this condition [22]; (c) have original data being independent from other studies; (d) have adequate data such as depression scales score as the main outcome measures. Search strategy We electronically searched six databases of Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, PubMed, Chinese National Knowledge Infrastructure (CNKI), Wanfang database and VIP information database. Studies reporting the use of brief psychotherapy strategies for depression in PD patients were identified. Reference lists from the resulting publications and reviews were used to identify further relevant publications. The following search strategy: 1. CBT 2. Cognitive behavioral therapy 3. Psychotherapy 4. Or/ Parkinson s disease 6. Parkinson disease 7. PD 8. Or/ Depression and (8 or 9). Data extraction and quality assessment For each study, information was carefully collected from all eligible publications, including (1) first author, year of publication, number of subjects, sex ratio (male/female), mean age of subjects, severity of PD, diagnostic criteria of depression and PD; (2) intervention characteristics of the trial groups (format, number of sessions) and control groups, main outcome measures. If the data for metaanalysis were missing or only expressed graphically, we tried to contact authors to inquire for further information or calculated by ourselves if available or excluded. If outcomes were presented from the studies at different time points, we extracted data from the last time point. For each comparison, we extracted data of mean value and standard deviation from each treatment and control group of every study. The validity of RCTs was assessed independently using the Cochrane Handbook for Systematic Reviews of Interventions. Statistical analysis We considered the main outcome measures as continuous data, and then were given an estimate of the combined overall effect sizes utilizing standard mean difference (SMD) with a random effects model. We used a random effects model rather than a fixed effects model because of this takes into account heterogeneity between multi-studies. SMD with its 95 % CI was used to assess the strength of efficacy of brief psychotherapy strategies for depression in PD patients. Publication bias was assessed by visual inspection of a funnel plot. Furthermore, to explore the impact of factors modifying on the outcome measures, we performed a stratified meta-analysis according to the following: different types of brief psychotherapy (CBT vs psychodynamic psychotherapy), quality of the studies, ethnicity and the treatments time. Heterogeneity across individual studies was calculated with I 2 statistical. All analysis was performed with Revman version 5.1. Probability value p \ 0.05 was considered significant. Results Study inclusion We identified 931 potentially relevant articles from six databases. After removal of duplicates, 229 records remained. After going through the titles and abstracts, 141 were excluded because they failed to meet the inclusion criteria. By reading the full text of the remaining 88 articles as having a possible relevance to the treatment of brief psychotherapy for the depression in PD patients, leaving 12 eligible studies satisfied the pre-established inclusion criteria [16, 23 33] (Fig. 1). Study characteristics The study basic characteristics are summarized in Table 1 for studies restricted to PD patients with depressive disorder. Studies were conducted in (9/11, 81.7 %), US (2/11, 18.2 %) and UK (1/11, 9.1 %), respectively. The 12 trials

4 Fig. 1 PRISMA 2009 flow diagram comprised a total of 766 people with an approximate mean age of 62 years. The number of participants randomized into the 12 trials included in this meta-analysis ranged from 10 [25] to 120[33] participants. Meanwhile, 48 % of the participants were male and the duration of treatment was ranged from 3 weeks [26] to10weeks[16]. These studies all had treatment of depression in PD patients as their primary goal. Hamilton rating scale for depression (HAMD) as the outcome measure was observed in 10 studies, Parkinson s disease questionnaire-39 (PDQ-39) was observed in 3 studies, adverse effects were just reported in 1 study. Montreal cognitive assessment (Moca) and General Wellbeing schedule (GWB) scales were reported in 2 studies, respectively. In terms of intervention, 6 studies evaluated CBT for depression in PD patients; the remaining adopted the psychodynamic psychotherapy in dpd patients. Study quality and publication bias Although all included studies claimed randomization, 3 articles described the method of random sequences generation (for example, random number generator, computer generated). Four trials gave information that allowed the assessment of whether an adequate concealment of allocation procedure was used. All the studies did not report the blinding of participants except three trials [22, 30, 33]. Only three trials [16, 25, 30] described intention-to-treat analyses (ITT). Non-selective reporting was found in 3 trials. Eight studies existed certain degree other potential threats to validity. Therefore, all of the included trials were deemed to have a moderate to severe risk of bias. The methodological quality of each study was summarizedintable2.

5 Table 1 Basic characteristics of included studies Study Criteria/country Design Basic data:m/f (n); age; duration, H Y scale Intervention Outcome measure Trial Control Trial Control p value Zhang [19] Zhang [20] Veazey [21] Zong [22] Dobkin [13] Deng [23] Huang [24] Mei [25] Chen [26] Cheng [27] CCMD-3 HAMD [18 CCMD-3 PHQ BAI USA CCMD-3 HAMD [20 DSM-IV USA CCMD-3 HAMD [18 CCMD-3-R HAMD C7 HAMD C 8 MMSE \ 24 HAMD [8 MoCA \26 CCMD-3 HAMD: RCT (random number table) and controlled nonblind parallel study RCT (odd/even numbers) and RCT (computer generated numbers) and controlled single blind study RCT (odd/even numbers) and M20/F15 (35), 64 ± 6 years,, M25/F15 (40), 63 ± 4 years, ; M5 (5), 66 ± 9.9 years, ; M16/F14 (30), ± 8.27 years,, M25/F16 (41); ± 9.89 years, 3.13 ± 3.36 years, 2.12 ± 0.9 M20/F15 (35),,, M39/F14 (53), 60.9 ± 9.6 years, years, M19/F15 (34), 65 ± 8 years,, M25/F15 (40), 63 ± 4 years, ; M5 (5), 75 ± 6.1 years, ; M15/F15 (30), ± 7.28 years,, M23/F16 (39), ± years, 2.54 ± 2.72 years, 2.16 ± 0.83 M19/F16 (35),,, M37/F16 (53), 60.5 ± 10.2 years, years, CBT:1 2 se/week?citanlopram: 20 mg/qm for 6 weeks Psychodynamic psychotherapy? conventional nursing CBT:one in-person CBT se, followed by eight weekly telephone se Psychodynamic psychotherapy for 3 weeks CBT: individual CBT se (60 75 m)? clinical monitor for 10 weeks CBT? Venlafaxine (75 mg/day) for Psychodynamic psychotherapy? Conventional nursing mode for 35,,, ,,, 2 3 Psychodynamic psychotherapy? medication therapy for 30, ± 8.49 years, 5.9 ± 3.68 years, M14/F16 (30); 62.5 ± 8.1 years,, 30, ± 9.20 years; 6.15 ± 4.22 years, M15/F15 (30); 62.0 ± 8.4 years,, Psychodynamic psychotherapy? conventional nursing mode for Psychodynamic psychotherapy:1 se/week (30 m)? medication therapy for 6 weeks Citanlopram: 20 mg/qm for 6 weeks Conventional nursing mode Support treatment: telephone se for Placebo for 3 weeks Clinical monitor via follow-up telephone calls for 7 weeks Venlafaxine: 75 mg/day for Conventional nursing mode for Medication therapy for Conventional nursing mode for Medication therapy for 6 weeks 1. HAMD 1. \ HAMD 1. \ PHQ 1. [ BAI 2. \ PDQ [ HAMD 1. \ GWB 2. \ HAMD 1. \ BDI 2. \ UPDRS 3. \ TR 4. \ HAMD 1. \ AE HAMD 1. \ Effective 2. \0.05 rate 1. HAMD 1. \ SDS 2. \ MMSE 3. \ Moca 4. \ HAMD 1. \ Moca 2. \ HAMD 1. \ CGI-SI 2. \ GWB 3. \ 0.05

6 Table 1 continued p value Study Criteria/country Design Basic data:m/f (n); age; duration, H Y scale Intervention Outcome measure Trial Control Trial Control 1. PSWQ 1. \ IUS 2. [ PDQ [0.05 No treatment for CBT: read the booklet based on the self-help resource for 17,,, 2.16 ± ,, 2.12 ± 0.90 RCT (random number table) and controlled nonblind parallel study HADS-A [8 ACE-R [83 UK Lawson [28] 1. HAMD 1. \ PDQ \0.01 M72/F48 (120), 49 ± 5 years,, CBT? Venlafaxine for Venlafaxine: mg. tid Du [29] HAMD [18 CCMD-3, Chinese classification of mental disorders-3; HAMD, Hamilton rating scale for depression; DSM, Diagnostic and Statistical Manual; Se, session; PHQ, Patient health questionnaire-9; BAI, Beck anxiety inventory; GWB, general well-being schedule; BDI, Beck depression inventory; TR, Treatment response; AE, adverse events; MMSE, Mini Mental State Examination; SDS, self-rating depression scale; Moca, Montreal cognitive assessment; CGI-SI, clinician s global impressions-severity of illness scale; HADS-A, Hospital Anxiety and Depression scale anxiety score; ACE-R, Addenbrooke s cognitive examination; PSWQ, Penn State Worry Questionnaire; IUS, intolerance of uncertainty scale; PDQ-39, Parkinson s disease questionnaire-39 Meta-analyses There were 10 studies reported the HAMD as the outcome measure with 724 participants included in the analysis. We pooled the whole data to process and found a significant difference in favor of the brief psychotherapy treatment compared with control groups (p \ , SMD = -1.45, 95 % CI to -0.91, Fig. 2). Nevertheless, inspection of the data showed that the heterogeneity for the analysis of HAMD between studies was high (s 2 = 0.68, v 2 = 95.83, p \ , I 2 = 91 %, Fig. 2). Consequently, we should interpret the pool result prudently. Removal of the outlier studies [25] led to more homogeneous results, but reduced the effect size by yielding a still significant pooled SMD of (95 % CI to -0.74, p \ ). Data on the clinician-rated PDQ-39 score was available from 3 trials with 160 participants included. We used a random effects model due to the 3 independent trials showed the severe heterogeneity in the consistency of the trial results (s 2 = 1.98, v 2 = 29.28, p \ , I 2 = 93 %, Fig. 3). However, we found no significant difference between brief psychotherapy and control groups (p = 0.31, SMD =-0.87, 95 % CI to 0.80, Fig. 3), suggesting that brief psychotherapy treatment could not contribute to improving the quality of the PD patients. In terms of the Moca scale, two studies showed certain effects of brief psychotherapy for improving the cognitive condition in dpd patients (p = 0.006, SMD = 0.52, 95 % CI 0.15 to 0.88; heterogeneity s 2 = 0.00, v 2 = 0.00, p = 0.99, I 2 = 0 %, Fig. 4). The funnel plot was roughly symmetric for the brief psychotherapy treatment on HAMD by visual inspection. Thus, funnel plots suggested no obvious publication bias (Fig. 5). Subgroup analyses Meta-analyses of studies that applied classic CBT or psychodynamic psychotherapy treatments both achieved significant overall effects (Z = 4.37, p \ ; Z = 4.11, p \ , respectively, Fig. 6). However, in the subgroup analysis for the outcome measure according to HAMD scale, the efficacy of psychodynamic psychotherapy treatments were better than CBT treatment (SMD =-2.02; SMD =-0.90, Fig. 6). Of the studies restricted to compared with US,the effect size of brief psychotherapy in was larger than in US (SMD =-1.49; SMD =-1.23, Fig. 7a). Of the whole comparisons, we compared the difference between high and low quality studies and detected that the effect of brief psychotherapy in low quality studies was more efficacious than in high quality studies (SMD =-1.54; SMD = -1.23, Fig. 7b). What is more, the impact of the length of

7 Table 2 The methodological quality of included studies based on the Cochrane handbook Study Zhang 2007 Zhang 2008 Veazey 2009 Zong 2009 Dobkin 2011 Deng 2011 Huang 2011 Mei 2011 Chen 2012 Cheng 2012 Lawson 2013 Du 2013 A???????????? B???? C??? D???? E???????????? F???? Total A, sequence generation; B, allocation concealment; C, blinding of participants, personnel and outcome assessors; D, incomplete outcome data; E, selective outcome reporting; F, other sources of bias;?, Yes; -, No;?, unclear ( Yes for a low risk of bias, No for a high risk of bias; Unclear otherwise) Fig. 2 Forest Plot of effect sizes for depression based on HAMD scale Fig. 3 Forest Plot of effect sizes for PDQ-39 Fig. 4 Forest Plot of effect sizes for Moca scale

8 Fig. 5 Bias assessment plot for the effect of brief psychotherapy on HAMD scale treatment also may contribute to discrepancy. The result showed that there was a trend for effect magnitude to be greater with the longer treatment (SMD =-1.50; SMD =-1.33, Fig. 7c. Time of brief psychotherapy therapy above 6 weeks was superior to studies with less than 6 weeks treatment. Discussion Summary of evidence This meta-analysis of 12 RCTs investigated the effect of brief psychotherapy on depression in PD patients with 766 participants. The results found that brief psychotherapy could evidently improve the HAMD and Moca score compared with control groups in dpd. Based on the HAMD scale, 10 studies with the total of 724 participants that met the inclusion criteria to process the analysis and the results indicated brief psychotherapy could improve the depression relevant symptoms compared with the control groups. Meanwhile, the result also demonstrated brief psychotherapy could ameliorate the cognitive function result from the Moca scale. However, there was no statistical difference in PDQ-39 improvement by the brief psychotherapy. To our best knowledge, it is probably that brief psychotherapy is beneficial in the treatment of depression symptom in PD patients as well as somewhat improve cognitive function. Subgroup analyses According to the different factors vary the effect size. We found that psychotherapy seems to more efficacious than CBT regarding depressive symptoms in PD patients. However, this difference reached significance only when the HAMD was used as an outcome measure. What is more, the effect size and sample size of studies were relatively small, limiting statistical power. To our knowledge, psychodynamic psychotherapy approaches are especially needed for individuals with depression and anxiety in PD patients who have a substandard response or intolerance to traditional antidepressant drug therapies [34]. CBT was defined mainly to focus on cognitive restructuring and behavioral activation, and has been shown by previous research to be one of the most effective interventions for depression [35]. CBT and psychodynamic psychotherapy may be considered the best options for psychological treatments for depression. But we did not identify any systematic reviews examining the effect of CBT versus psychodynamic psychotherapy in dpd patients. Subgroup analyses of versus USA showed the pooled results of studies from (-1.49) had a stronger significant effect than those including participants from USA (-1.23). There were several possibilities which might account for the result. First, PD or depression is a complex disease which is related to genetic factors. Hence, it is possible that different genetic background may result in this discrepancy [36]. Second, the number of participants from US is dramatically less than, which might also result in certain bias. For subgroup analysis based on studies quality, significant effect was found in both high and low studies. However, the effect of brief psychotherapy in low quality studies (-1.54) was more efficacious than in high quality studies (-1.23). The result suggested the quality of studies was one of the determinant factors influenced the consequence. When stratified by the length of treatment, we found that time of brief psychotherapy treatment above 6 weeks was superior to studies with less than 6 weeks treatment. Limitations The methodological quality of the included studies was highly variable and not optimal. Nearly all of the included studies had an overall assessment as high risk of bias, so we could not exclude that our results may be biased. Some studies indicated that statistically significant % exaggeration of treatment efficacy when results of lowerquality trials were pooled [37]. It might be that high quality studies have lower variance then the effects will appear larger, or improvement in the quality of reporting studies will also help reduce bias when such trials are included in systematic reviews. Consequently, we recommend that future studies use and report adequate randomization methods, sufficient blinding of outcome assessors, and intent-to-treat analyses. Moreover, the number of studies in subgroup analysis was relatively small and may have lacked statistical power to detect smaller effect sizes. None

9 Fig. 6 Forest plot of subgroup analysis (psychosocial treatments vs cognitive behavioral therapy) for HAMD scale of the studies are reported on adverse events or on suicide inclination, suicide attempts, or suicides. Only one of the included trials included assessments after the cessation of treatment. Therefore, the evidence for long-term effects of brief psychotherapy seems to be lacking. Moreover, all of the included studies indicated that all participants continued to maintain stable medical regimens such as antiparkinsonian treatment. However, none of the study displayed the type, dosage and regimen of such health- care. To our knowledge, the potential involvement of dopamine in the pathogenesis of depression in patients with PD suggests that dopaminergic treatment might improve depression in these individuals [38]. In addition, pramipexole and other dopamine agonists, such as ropinirole, might also have antidepressant properties [39]. Finally, none of the studies have monitored the treatment fidelity of brief psychotherapy in this meta-analysis. There is evidence that the effectiveness of therapeutic interventions decreases as therapies move from university research studies into routine clinical practice [40]. Therefore, treatment integrity or fidelity checks are needed to monitor the extent to which treatments are delivered appropriately. No doubt, the need for further development of brief psychotherapy measures to provide the needed technology for advancing brief psychotherapy dissemination and implementation has recently been highlighted [41]. What is more, skilled therapists are additional factors to consider. There is evidence that paraprofessionals, working under supervision following minimal training, can deliver effective manualized brief psychotherapy, and this strategy has been used to deliver interventions for depression [42]. Implication for further studies This meta-analysis of RCTs mainly focuses on the efficacy of brief psychotherapy therapy for dpd patients. According to our meta-analysis, patients receiving brief psychotherapy therapy exhibit significant ameliorate in their depression symptoms as evidenced by improvements in their HAMD scores. However, improvement in the methodological quality of RCTs is critical for later trials and more methodologically rigorous studies are needed in this field, and sample size calculation should be conducted before enrollment. Next, the HAMD might not be adequate instruments to quantify the efficacy of interventions for depression. Other assessment tools could also demonstrate a more or less effect of given intervention for depression, such as Montgomery Asberg depression rating scale (MADRS), self-rating depression scale (SDS), Beck depression inventory (BDI), Quick inventory of depressive symptomatology (QIDS). Furthermore, severity of depression as measured by the HAMD score has failed to predict suicide attempts and inclinations. For this reason, there is a need for trials assessing and reporting more clinically relevant outcome measures to comprehensive understanding the details of the patients. Future research should be conducted with longer follow-up, low risk of bias and report on adverse events, suicide inclination.

10 the study participants. The author(s) received no financial support for the research, authorship, and/or publication of this article. The authors declare that they have no com- Conflict of interest peting interests. References Fig. 7 Subgroup analysis for the HAMD outcome. a The impact of country on the estimate of the outcome; b the quality of studies on the estimate of the outcome; c the impact of treatment time on the estimate of the outcome. The vertical error bars represent the effect size (SMD) for the individual estimates Furthermore, there may be a need for a new assessment method other than the HAMD to assess depressive symptoms. Conclusion We found that brief psychotherapy therapy was probable effective in the management of depression in PD patients. But one reason to undermine the validity of findings is high clinical heterogeneity and low methodological quality of the included trials. Therefore, well-designed, randomized, placebo-controlled clinical trials are still needed to further evaluate the brief psychotherapy therapy for dpd due to the generally low methodological quality of the included studies. Acknowledgments We gratefully acknowledge Wen Wen Wang for his help in guiding and revising the manuscript. We also thank all 1. Chaudhuri KR, Schapira AH (2009) Non-motor symptoms of Parkinson s disease: dopaminergic pathophysiology and treatment. Lancet Neurol 8(5): Black KJ (2011) A new (old) treatment option for depression in Parkinson s disease. Am J Psychiatry 168(10): Menza M, Dobkin RD, Marin H et al (2009) The impact of treatment of depression on quality of life, disability and relapse in patients with Parkinson s disease. Mov Disord 24(9): Carod-Artal FJ, Ziomkowski S, Mourão Mesquita H et al (2008) Anxiety and depression: main determinants of health-related quality of life in Brazilian patients with Parkinson s disease. Parkinsonism Relat Disord 14(2): Aarsland D, Påhlhagen S, Ballard CG et al (2011) Depression in Parkinson disease epidemiology, mechanisms and management. Nat Rev Neurol 8(1): Menza M, Dobkin RD, Marin H et al (2009) A controlled trial of antidepressants in patients with Parkinson disease and depression. Neurology 72(10): Troeung L, Egan SJ, Gasson N (2013) A meta-analysis of randomised placebo-controlled treatment trials for depression and anxiety in Parkinson s disease. PLoS One 8(11):e Richard IH, McDermott MP, Kurlan R et al (2012) A randomized, double-blind, placebo-controlled trial of antidepressants in Parkinson disease. Neurology 78(16): Price A, Rayner L, Okon-Rocha E et al (2011) Antidepressants for the treatment of depression in neurological disorders: a systematic review and meta-analysis of randomised controlled trials. J Neurol Neurosurg Psychiatry 82(8): Veazey C, Aki SO, Cook KF et al (2005) Prevalence and treatment of depression in Parkinson s disease. J Neuropsychiatry Clin Neurosci 17(3): van der Marck MA, Munneke M, Mulleners W et al (2013) Integrated multidisciplinary care in Parkinson s disease: a non-randomised, controlled trial (IMPACT). Lancet Neurol 12(10): Oehlberg K, Barg FK, Brown GK et al (2008) Attitudes regarding the etiology and treatment of depression in Parkinson s disease: a qualitative study. J Geriatr Psychiatry Neurol 21(2): Brewin CR (1996) Theoretical foundations of cognitive-behavior therapy for anxiety and depression. Annu Rev Psychol 47: Schildmann EK, Higginson IJ (2011) Evaluating psycho-educational interventions for informal carers of patients receiving cancer care or palliative care: strengths and limitations of different study designs. Palliat Med 25(4): Parker B, Turner W (2013) Psychoanalytic/psychodynamic psychotherapy for children and adolescents who have been sexually abused. Cochrane Database Syst Rev 7:CD Dobkin RD, Menza M, Allen LA et al (2011) Cognitive-behavioral therapy for depression in Parkinson s disease: a randomized, controlled trial. Am J Psychiatry 168(10): Dobkin RD, Menza M, Allen LA et al (2011) Telephone-based cognitive-behavioral therapy for depression in Parkinson disease. J Geriatr Psychiatry Neurol 24(4): Mohr DC, Ho J, Duffecy J et al (2012) Effect of telephoneadministered vs face-to-face cognitive behavioral therapy on adherence to therapy and depression outcomes among primary care patients: a randomized trial. JAMA 307(21):

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