Comparative efficacy and tolerability of pharmacological and somatic interventions in adult patients with treatment-resistant depression: a systematic review and network meta-analysis.

OBJECTIVE: Major depressive disorder (MDD) affects about 10-15% of the general population in a lifetime. A considerable number of patients fail to achieve full symptom remission despite adequate treatment and are considered treatment resistant (TRD). The current study compared the relative efficacy and tolerability of pharmacological and somatic TRD interventions by means of a Bayesian network meta-analysis. RESEARCH DESIGN AND METHODS: An electronic literature search of MEDLINE, MEDLINE In-Process, EMBASE, PsycInfo, EconLit and Cochrane Library databases for trials published between September 2003 and September 2014 was conducted. Key outcomes extracted were disease severity change from baseline, response and remission rates at various timepoints and discontinuation due to adverse events. RESULTS: Of the 3876 abstracts identified, 31 publications/randomised controlled trials (RCTs) were included in the analysis; 19 RCTs investigating 13 pharmacological interventions and 12 RCTs investigating electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS). The evidence synthesis investigating efficacy outcomes of TRD treatments demonstrated superior efficacy for ketamine compared to pharmacological and somatic interventions at 2 weeks after treatment initiation. At 4, 6 and 8 weeks, quetiapine augmentation (800 mg/day) and risperidone augmentation were found to be the first and second best treatments, respectively. Networks were small for response rate and remission rate outcomes at most timepoints. The most tolerable treatment was lamotrigine augmentation showing a comparable profile to placebo/sham. CONCLUSIONS: This analysis revealed scarcity of long-term data on sustained remission that would allow a comparative long-term efficacy assessment. Key limitations of the analysis can be considered the search timeframe and the use of mapping formula for the depression scores.

Characterization of treatment resistant depression episodes in a cohort of patients from a US commercial claims database.

CONTEXT: Treatment Resistant Depression (TRD) is a significant and burdensome health concern. OBJECTIVE: To characterize, compare and understand the difference between TRD and non-TRD patients and episodes in respect of their episode duration, treatment patterns and healthcare resource utilization. DESIGN AND SETTING: Patients between 18 and 64 years with a new diagnosis of major depressive disorder (MDD) and without a previous or comorbid diagnosis of schizophrenia or bipolar disease were included from PharMetrics Integrated Database, a claims database of commercial insurers in the US. Episodes of these patients in which there were at least two distinct failed regimens involving antidepressants and antipsychotics were classified as TRD. PATIENTS: 82,742 MDD patients were included in the analysis; of these patients, 125,172 episodes were identified (47,654 of these were drug-treated episodes). MAIN OUTCOME MEASURES: Comparison between TRD and non-TRD episodes in terms of their duration, number and duration of lines of treatment, comorbidities, and medical resource utilization. RESULTS: Of the treated episodes, 6.6% (N = 3,134) met the criteria for TRD. The median time to an episode becoming TRD was approximately one year. The mean duration of a TRD episode was 1,004 days (vs. 452 days for a non-TRD episode). More than 75% of TRD episodes had at least four lines of therapy; half of the treatment regimens included a combination of drugs. Average hospitalization costs were higher for TRD than non-TRD episodes: $6,464 vs. $1,734, as were all other health care utilization costs. CONCLUSIONS: While this study was limited to relatively young and commercially covered patients, used a rigorous definition of TRD and did not analyze for cause or consequence, the results highlight high unmet medical need and burden of TRD on patients and health care resources.