Trina E. Chang

The Future of Psychopharmacology of Depression

There are clear limitations to the currently approved pharmacotherapies of depression, including the fact that they are all essentially monoamine-based, have modest efficacy and a relatively slow onset of efficacy, and suffer from significant tolerability issues, particularly in the long term, including sexual dysfunction, weight gain, and cognitive impairments. This article reviews some of the most promising novel mechanisms that are not represented in compounds currently approved for depression in either the United States or Europe and that may represent the future of the psychopharmacologic treatment of depression, potentially addressing some of the efficacy and tolerability issues of antidepressants on the market. These potential antidepressant treatments include the multimodal serotonergic agents, the triple uptake inhibitors, the neurokinin-based novel therapies, the glutamatergic treatments, the nicotinic receptor-based treatments, the neurogenesis-based treatments, and antiglucocorticoid therapies. Some of these mechanisms appear to be more advanced in terms of drug development than others, but they all contribute to the global effort to develop more effective and better tolerated treatments for major depressive disorder.

Clinical Outcomes in Measurement-based Treatment (Comet): a trial of depression monitoring and feedback to primary care physicians.

Despite the availability of effective treatments for depression, many patients under the care of primary care physicians do not achieve remission. Clinical Outcomes in Measurement‐based Treatment (COMET) was designed to assess whether communicating patient‐reported depression symptom severity to primary care physicians affects patient outcomes at 6 months.

Using online social media, Facebook, in screening for major depressive disorder among college students

This study explored the feasibility of using Internet social networking media in an online program for Major Depressive Disorder (MDD) screening and psychoeducation targeting college students. A Facebook advertisement targeted students at five colleges in the United States to complete a mental health research survey that screened for MDD using the Patient Health Questionnaire-9 (PHQ-9). Students who screened positive for MDD were offered an eight- week follow-up survey. Of the 259 students who consented to participate in the study, 26.7% screened positive for MDD, while only 14.2% were receiving treatment. The use of Facebook to advertise for online screening for MDD required very little start-up time, and the average cost was

Near-Infrared Transcranial Radiation for Major Depressive Disorder: Proof of Concept Study

11.45 per subject recruited. It is feasible to use online, commercially available social networking media such as Facebook for online screening for MDD among college students. However, conducting online screening and offering treatment resources alone did not increase treatment rate in this population.

Ketamine augmentation for outpatients with treatment-resistant depression: Preliminary evidence for two-step intravenous dose escalation

Transcranial near-infrared radiation (NIR) is an innovative treatment for major depressive disorder (MDD), but clinical evidence for its efficacy is limited. Our objective was to investigate the tolerability and efficacy of NIR in patients with MDD. We conducted a proof of concept, prospective, double-blind, randomized study of 6 sessions of NIR versus sham treatment for patients with MDD, using a crossover design. Four patients with MDD with mean age 47 ± 14 (SD) years (1 woman and 3 men) were exposed to irradiance of 700 mW/cm2 and a fluence of 84 J/cm2 for a total NIR energy of 2.40 kJ delivered per session for 6 sessions. Baseline mean HAM-D17 scores decreased from 19.8 ± 4.4 (SD) to 13 ± 5.35 (SD) after treatment (t = 7.905; df = 3; P = 0.004). Patients tolerated the treatment well without any serious adverse events. These findings confirm and extend the preliminary data on NIR as a novel intervention for patients with MDD, but further clinical trials are needed to better understand the efficacy of this new treatment. This trial is registered with ClinicalTrials.gov NCT01538199.

The Engagement Interview Protocol (EIP): improving the acceptance of mental health treatment among Chinese immigrants.

Objective: Preliminary evidence supports the safety and efficacy of subanesthetic ketamine as an experimental antidepressant, although its effects are often not sustained beyond one week. Studies are lacking that have examined the sustained effects of escalating ketamine doses as augmentation in outpatients with treatment-resistant depression. Therefore, the aims of this study were twofold: (1) to assess the safety and antidepressant efficacy of two-step, repeated-dose ketamine augmentation and (2) to assess the duration of ketamine’s antidepressant efficacy as augmentation to ongoing antidepressant pharmacotherapy for 3 months after the final infusion. Methods: Fourteen patients with treatment-resistant depression were eligible to receive augmentation with six open-label intravenous ketamine infusions over 3 weeks. For the first three infusions, ketamine was administered at a dose of 0.5 mg/kg over 45 minutes; the dose was increased to 0.75 mg/kg over 45 minutes for the subsequent three infusions. The primary outcome measure was response (as measured on Hamilton Depression Rating Scale–28 items). Results: After the completion of three ketamine infusions, 7.1% (1/14) responded; after all six ketamine infusions, 41.7% (5/12) completers responded and 16.7% (2/12) remitted. Intent-to-treat response and remission rates at the end of the final infusion were 35.7% (5/14) and 14.3% (2/14), respectively. However, all but one responder relapsed within 2 weeks after the final infusion. Conclusion: Repeated, escalating doses of intravenous ketamine augmentation were preliminarily found to be feasible, efficacious and well tolerated. Interaction with concomitant medications and elevated level of treatment resistance are possible factors for non-response.

Web-Based Depression Screening and Psychiatric Consultation for College Students: A Feasibility and Acceptability Study

Many depressed Chinese immigrants are unfamiliar with Western psychiatric terminology and have high levels of stigma toward psychiatric illnesses, making it difficult to engage them into psychiatric treatment. We have designed the Engagement Interview Protocol (EIP), a semi-standardized protocol that incorporates cultural components to a standard psychiatric evaluation. The EIP elicits patients’ narratives and uses anthropological questions to explore patients’ illness beliefs, which are integrated with patients’ information on medical and psychiatric history, psychosocial background and mental status examination so that treatment options can be negotiated in a culturally sensitive manner. In our field testing on depressed Chinese immigrants, the EIP model was found to be a practical tool that can be completed within the allotted one-hour time frame and was highly effective in facilitating the enrollment of patients in treatment for depression. The EIP is a concise, time-effective, user-friendly protocol that can be used both in research and real-world clinical settings with diverse patient populations.

Assessing the adequacy of past antidepressant trials: a clinician's guide to the antidepressant treatment response questionnaire.

Background. A steady rise in the prevalence of depression among college students has negatively affected student quality of life. This study investigates the feasibility and acceptability of a Web-based model, including Skype, to screen and provide psychiatric consultation to depressed college students. Methods. Students completed the 9-item Patient Health Questionnaire (PHQ-9) online; those who screened positive (PHQ-9 ≥ 10) or endorsed any level of suicidal ideation were offered Web-based psychiatric consultation using Skype. After the consultation, students filled out a 7-item satisfaction questionnaire to report on the acceptability of this Web-based method. Results. A total of 972 students consented to the online depression screening and 285 screened positive. Of those, 69 students consented and 17 students successfully completed the psychiatric consultation via Skype. Thirteen (76.4%) students found the interview useful in helping them understand their depression. Fifteen (88.2%) students thought that psychologists and psychiatrists could successfully see patients via videoconferencing. Conclusions. Current online technologies can provide depression screening and psychiatric consultation to college students; those who participated reported a positive experience. Future studies will need to address the low levels of participation among college students and attract students who are underserved, as well as use a videoconferencing platform that adequately protects data confidentiality.

Cross-Cultural Aspects of Depression Management in Primary Care

Many depressed patients do not remit on antidepressant medication despite an adequate dosage and a sufficient duration of treatment.1 This has spawned endeavors to define treatment-resistant depression as a depressive episode that has shown insufficient response to 1 or more adequate trials of an antidepressant.1 What constitutes insufficient, inadequate, or partial response is still a matter of debate. Recently, an operational classification of degree of treatment resistance was proposed,2 with categorical distinctions defined by the percent symptom reduction from baseline as follows: nonresponse, < 25% reduction; partial response, 25%–49% reduction; and response without remission, ≥ 50% reduction but without achievement of remission.1 To determine the adequacy and outcome of treatment in a way that can be communicated among clinicians and researchers, it is crucial to employ a reliable and valid instrument. While historical rating of treatment is not as accurate as a prospective trial, there are many instances in which a decision is needed before the next trial is carried out. Several tools have been proposed, such as the Antidepressant Treatment History Form (ATHF),3 the Harvard Antidepressant Treatment History (HATH),4 and the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (ATRQ).1,5 The ATHF and HATH have the advantage of integrating clinical judgment in the assessment of treatment resistance, but these questionnaires are quite burdensome.5 The ATRQ (Appendix 1) and accompanying questions are meant to provide clinicians with a user-friendly tool for assessment of prior treatment. It is often the case that a patient remembers whether a past treatment was somewhat helpful, although it is frequently difficult for him or her to remember exactly which antidepressant was taken, how long it was taken, and at what dose. However, it is important that the clinician explore past trials thoroughly using a systematic approach in order to characterize the adequacy of the trial and the degree of improvement. The clinician version of the ATRQ1,5 examines the adequacy of duration and dose of prior and current antidepressant treatments in a step-by-step procedure. It cannot be emphasized enough that, when assessing the duration and dose of clinical trials of antidepressants, clinicians must always inquire about adherence to each treatment trial. In addition, the ATRQ assesses the degree of improvement (in the most efficacious trial or in all trials during the current episode, depending on the version of the instrument) on a scale from 0% (not improved at all) to 100% (completely improved) (Table 1). The previous treatment may have been monotherapy, an augmentation trial, a trial of 2 antidepressants (combination therapy), or a switch to another antidepressant. Our group has adopted conventions to define resistance to each of these approaches. At the outset it is noted that the doses and durations required for adequate treatment are based on expert consensus1 rather than systematic research. We define an adequate monotherapy trial as a trial lasting at least 6 weeks at a minimum effective dose. In the context of this initial trial, the adequate duration for augmentation or combination treatment is at least 3 weeks. However, a combination trial from the onset (ie, starting with 2 drugs together) must be 6 weeks. Six weeks is also required for a switch to a different antidepressant. Each of these trials is considered a new trial. An increase in dose for at least 4 weeks represents optimization and is not considered a new or separate trial. However, if remission is later followed by relapse, a dose increase represents a new trial for the new episode. We recognize that the conventions used to define adequate dose and duration are not established and that other conventions, for example, a duration of 12 weeks, might be preferred. The ATRQ can be adapted to accommodate various definitions of dose and duration. Likewise, the threshold of resistance in terms of percent response may vary, depending on the questions being asked within a given clinical trial.

Differential impact of isolated psychotic symptoms on treatment outcome of major depressive disorder in the STAR*D cohort of Whites, Blacks and Latinos

Major depressive disorder (MDD) is a prevalent illness in minority populations. Minority patients with MDD are often unrecognized and untreated. This review examines promising interventions to address MDD in primary care settings, where minority groups are more likely to seek care. Since 2010, eleven interventions have been developed to address patient-specific and provider-specific barriers, many of which are adaptations of the collaborative care model. Other promising interventions include cultural tailoring of the collaborative care model, as well as the addition of telepsychiatry, motivational interviewing, cultural consultation, and innovations in interpreting. Overall, collaborative care was found feasible and improved satisfaction and treatment engagement of depressed minority patients in primary care. It remains inconclusive whether these newer intervention models improve MDD treatment outcomes. Future research will be needed to establish the effectiveness of these intervention models in improving the treatment outcomes of minority populations with MDD.