Tachyphylaxis in major depressive disorder: A review of the current state of research.

BACKGROUND: Patients with major depressive disorder (MDD) often experience a re-emergence or worsening of symptoms despite ongoing treatment with previously effective antidepressant pharmacotherapy. This lost or reduced antidepressant response during maintenance, referred to as tachyphylaxis, negatively impacts treatment outcomes and quality of life for patients with MDD. This review assesses the prevalence of antidepressant tachyphylaxis as well as the evidence for interventions to manage it. METHODS: We searched PubMed/Medline for the relevant clinical trials and meta-analyses on antidepressant tachyphylaxis up to January 2017. Search terms included "depression" paired with "treatment" (n = 186,674), "tachyphylaxis" paired with "depression" (n = 112), "tachyphylaxis" paired with "major depressive disorder" (n = 21), and "antidepressant" paired with "tachyphylaxis" (n = 68). Studies were included if they reported on a clinical trial or meta-analysis exploring tachyphylaxis in MDD and were excluded if the sample population did not have a primary DSM diagnosis of MDD. RESULTS: Rates of tachyphylaxis varied from 9% to 57% depending on the patient population and duration of follow-up. Limited evidence suggests potentially beneficial strategies for managing tachyphylaxis, including change in antidepressant dosing, switch of class of antidepressant medication, augmentation or combination pharmacotherapy, and psychotherapy. LIMITATIONS: Studies of antidepressant tachyphylaxis are largely heterogeneous in nature and employ strict inclusion/exclusion criteria; thus, these findings may not be generalizable to all depressed populations. CONCLUSION: Few established treatment strategies exist to manage antidepressant tachyphylaxis. Further interventional research is needed to provide symptomatic relief for patients with tachyphylaxis in MDD.

The association of psychedelic use and opioid use disorders among illicit users in the United States.

BACKGROUND: Preliminary studies show psychedelic compounds administered with psychotherapy are potentially effective and durable substance misuse interventions. However, little is known about the association between psychedelic use and substance misuse in the general population. This study investigated the association between psychedelic use and past year opioid use disorders within illicit opioid users. METHODS: While controlling for socio-demographic covariates and the use of other substances, the relationship between classic psychedelic use and past year opioid use disorders was analyzed within 44,000 illicit opioid users who completed the National Survey on Drug Use and Health from 2008 to 2013. RESULTS: Among respondents with a history of illicit opioid use, psychedelic drug use is associated with 27% reduced risk of past year opioid dependence (weighted risk ratio = 0.73 (0.60-0.89) p = 0.002) and 40% reduced risk of past year opioid abuse (weighted risk ratio = 0.60 (0.41-0.86) p = 0.006). Other than marijuana use, which was associated with 55% reduced risk of past year opioid abuse (weighted risk ratio = 0.45 (0.30-0.66) p < 0.001), no other illicit drug was associated with reduced risk of past year opioid dependence or abuse. CONCLUSION: Experience with psychedelic drugs is associated with decreased risk of opioid abuse and dependence. Conversely, other illicit drug use history is largely associated with increased risk of opioid abuse and dependence. These findings suggest that psychedelics are associated with positive psychological characteristics and are consistent with prior reports suggesting efficacy in treatment of substance use disorders.

Effects of 3,4-Methylenedioxymethamphetamine on Patient Utterances in a Psychotherapeutic Setting.

3,4-Methylenedioxymethamphetamine (MDMA) administered as an adjunct to talk therapy influences patient speech content and increases improvement in treatment-resistant posttraumatic stress disorder (PTSD). Data came from the recordings of Mithoefer et al. (2011). In the third therapeutic session studied, patients were assigned, double blind, to an MDMA or a placebo group. Condition-blind scorers listened to therapy recordings and scored utterances where patients initiated topics that were empathic (regarding others' emotions), entactic (requesting or appreciating physical touch), or ensuic (describing a change in their sense of themselves). Patients who received MDMA produced high levels of ensuic, empathic, and entactic utterances compared with those who received the placebo. Interrater discourse scoring was reliable. The relationship between the number of scored utterances and the Clinician Administered PTSD Scale scores measuring PTSD severity after the treatment was significant, and reanalysis grouped bimodally into "many" or "few" such utterances remained significant. MDMA assisted these patients in having meaningful and disorder-resolving thoughts and discourse in talk therapy.