Blunted amygdala activity is associated with depression severity in treatment-resistant depression.

Up to 50% of individuals with major depressive disorder (MDD) do not recover after two antidepressant medication trials, and therefore meet the criteria for treatment-resistant depression (TRD). Mindfulness-based cognitive therapy (MBCT) is one promising treatment; however, the extent to which MBCT influences clinical outcomes relative to baseline neural activation remains unknown. In the present study we investigated baseline differences in amygdala activation between TRD patients and healthy controls (HCs), related amygdala activation to depression symptoms, and examined the impacts of MBCT and amygdala activation on longitudinal depression outcomes. At baseline, TRD patients (n = 80) and HCs (n = 37) participated in a functional magnetic resonance imaging task in which they identified either the emotion (affect labeling) or the gender (gender labeling) of faces, or passively viewed faces (observing). The TRD participants then completed eight weeks of MBCT or a health enhancement program (HEP). Relative to HCs, the TRD patients demonstrated less amygdala activation during affect labeling, and marginally less during gender labeling. Blunted amygdala activation in TRD patients during affect labeling was associated with greater depression severity. MBCT was associated with greater depression reductions than was HEP directly following treatment; however, at 52 weeks the treatment effect was not significant, and baseline amygdala activation across the task conditions predicted depression severity in both groups. TRD patients have blunted amygdala responses during affect labeling that are associated with greater concurrent depression. Furthermore, although MBCT produced greater short-term improvements in depression than did HEP, overall baseline amygdala reactivity was predictive of long-term clinical outcomes in both groups.

A Randomized Controlled Trial of Mindfulness-Based Cognitive Therapy for Treatment-Resistant Depression.

BACKGROUND: Due to the clinical challenges of treatment-resistant depression (TRD), we evaluated the efficacy of mindfulness-based cognitive therapy (MBCT) relative to a structurally equivalent active comparison condition as adjuncts to treatment-as-usual (TAU) pharmacotherapy in TRD. METHODS: This single-site, randomized controlled trial compared 8-week courses of MBCT and the Health Enhancement Program (HEP), comprising physical fitness, music therapy and nutritional education, as adjuncts to TAU pharmacotherapy for outpatient adults with TRD. The primary outcome was change in depression severity, measured by percent reduction in the total score on the 17-item Hamilton Depression Rating Scale (HAM-D17), with secondary depression indicators of treatment response and remission. RESULTS: We enrolled 173 adults; mean length of a current depressive episode was 6.8 years (SD = 8.9). At the end of 8 weeks of treatment, a multivariate analysis showed that relative to the HEP condition, the MBCT condition was associated with a significantly greater mean percent reduction in the HAM-D17 (36.6 vs. 25.3%; p = 0.01) and a significantly higher rate of treatment responders (30.3 vs. 15.3%; p = 0.03). Although numerically superior for MBCT than for HEP, the rates of remission did not significantly differ between treatments (22.4 vs. 13.9%; p = 0.15). In these models, state anxiety, perceived stress and the presence of personality disorder had adverse effects on outcomes. CONCLUSIONS: MBCT significantly decreased depression severity and improved treatment response rates at 8 weeks but not remission rates. MBCT appears to be a viable adjunct in the management of TRD.

Critical analysis of the efficacy of meditation therapies for acute and subacute phase treatment of depressive disorders: a systematic review.

BACKGROUND: Recently, the application of meditative practices to the treatment of depressive disorders has met with increasing clinical and scientific interest, owing to a lower side-effect burden, potential reduction of polypharmacy, and theoretical considerations that such interventions may target some of the cognitive roots of depression. OBJECTIVE: We aimed to determine the state of the evidence supporting this application. METHODS: Randomized controlled trials of techniques meeting the Agency for Healthcare Research and Quality definition of meditation, for participants having clinically diagnosed depressive disorders, not currently in remission, were selected. Meditation therapies were separated into praxis (i.e., how they were applied) components, and trial outcomes were reviewed. RESULTS: 18 studies meeting the inclusion criteria were identified, encompassing 7 distinct techniques and 1173 patients. Mindfulness-Based Cognitive Therapy comprised the largest proportion of studies. Studies including patients having acute major depressive episodes (n = 10 studies), and those with residual subacute clinical symptoms despite initial treatment (n = 8), demonstrated moderate to large reductions in depression symptoms within the group, and relative to control groups. There was significant heterogeneity of techniques and trial designs. CONCLUSIONS: A substantial body of evidence indicates that meditation therapies may have salutary effects on patients having clinical depressive disorders during the acute and subacute phases of treatment. Owing to methodologic deficiencies and trial heterogeneity, large-scale, randomized controlled trials with well-described comparator interventions and measures of expectation are needed to clarify the role of meditation in the depression treatment armamentarium.

Mindfulness-based cognitive therapy (MBCT) versus the health-enhancement program (HEP) for adults with treatment-resistant depression: a randomized control trial study protocol.

BACKGROUND: Major depressive disorder (MDD) is the leading cause of disability in the developed world, yet broadly effective treatments remain elusive. Up to 40% of patients with depression are unresponsive to at least two trials of antidepressant medication and thus have "treatment-resistant depression" (TRD). There is an urgent need for cost-effective, non-pharmacologic, evidence-based treatments for TRD. Mindfulness-Based Cognitive Therapy (MBCT) is an effective treatment for relapse prevention and residual depression in major depression, but has not been previously studied in patients with TRD in a large randomized trial. METHODS/DESIGN: The purpose of this study was to evaluate whether MBCT is an effective augmentation of antidepressants for adults with MDD who failed to respond to standard pharmacotherapy. MBCT was compared to an active control condition, the Health-Enhancement Program (HEP), which incorporates physical activity, functional movement, music therapy and nutritional advice. HEP was designed as a comparator condition for mindfulness-based interventions to control for non-specific effects. Originally investigated in a non-clinical sample to promote stress reduction, HEP was adapted for a depressed population for this study. Individuals age 18 and older with moderate to severe TRD, who failed to respond to at least two trials of antidepressants in the current episode, were recruited to participate. All participants were taking antidepressants (Treatment as usual; TAU) at the time of enrollment. After signing an informed consent, participants were randomly assigned to either MBCT or HEP condition. Participants were followed for 1 year and assessed at weeks 1-7, 8, 24, 36, and 52. Change in depression severity, rate of treatment response and remission after 8 weeks were the primary outcomes measured by the clinician-rated Hamilton Depression Severity Rating (HAM-D) 17-item scale. The participant-rated Quick Inventory of Depression Symptomology (QIDS-SR) 16-item scale was the secondary outcome measure of depression severity, response, and remission. DISCUSSION: Treatment-resistant depression entails significant morbidity and has few effective treatments. We studied the effect of augmenting antidepressant medication with MBCT, compared with a HEP control, for patients with TRD. Analyses will focus on clinician and patient assessment of depression, participants' clinical global impression change, employment and social functioning scores and quality of life and satisfaction ratings. TRIAL REGISTRATION: ClincalTrials.gov identifier: NCT01021254.

Dysfunctional Cortical Gradient Topography in Treatment-Resistant Major Depressive Disorder.

BACKGROUND: Treatment-resistant depression (TRD) refers to patients with major depressive disorder who do not remit after 2 or more antidepressant trials. TRD is common and highly debilitating, but its neurobiological basis remains poorly understood. Recent neuroimaging studies have revealed cortical connectivity gradients that dissociate primary sensorimotor areas from higher-order associative cortices. This fundamental topography determines cortical information flow and is affected by psychiatric disorders. We examined how TRD impacts gradient-based hierarchical cortical organization. METHODS: In this secondary study, we analyzed resting-state functional magnetic resonance imaging data from a mindfulness-based intervention enrolling 56 patients with TRD and 28 healthy control subjects. Using gradient extraction tools, baseline measures of cortical gradient dispersion within and between functional brain networks were derived, compared across groups, and associated with graph theoretical measures of network topology. In patients, correlation analyses were used to associate measures of cortical gradient dispersion with clinical measures of anxiety, depression, and mindfulness at baseline and following the intervention. RESULTS: Cortical gradient dispersion was reduced within major intrinsic brain networks in patients with TRD. Reduced cortical gradient dispersion correlated with increased network degree assessed through graph theory-based measures of network topology. Lower dispersion among default mode, control, and limbic network nodes related to baseline levels of trait anxiety, depression, and mindfulness. Patients' baseline limbic network dispersion predicted trait anxiety scores 24 weeks after the intervention. CONCLUSIONS: Our findings provide preliminary support for widespread alterations in cortical gradient architecture in TRD, implicating a significant role for transmodal and limbic networks in mediating depression, anxiety, and lower mindfulness in patients with TRD.

Mindfulness-based cognitive therapy: theory and practice.

Mindfulness-based cognitive therapy (MBCT) incorporates elements of cognitive-behavioural therapy with mindfulness-based stress reduction into an 8-session group program. Initially conceived as an intervention for relapse prevention in people with recurrent depression, it has since been applied to various psychiatric conditions. Our paper aims to briefly describe MBCT and its putative mechanisms of action, and to review the current findings about the use of MBCT in people with mood and anxiety disorders. The therapeutic stance of MBCT focuses on encouraging patients to adopt a new way of being and relating to their thoughts and feelings, while placing little emphasis on altering or challenging specific cognitions. Preliminary functional neuroimaging studies are consistent with an account of mindfulness improving emotional regulation by enhancing cortical regulation of limbic circuits and attentional control. Research findings from several randomized controlled trials suggest that MBCT is a useful intervention for relapse prevention in patients with recurrent depression, with efficacy that may be similar to maintenance antidepressants. Preliminary studies indicate MBCT also shows promise in the treatment of active depression, including treatment-resistant depression. Pilot studies have also evaluated MBCT in bipolar disorder and anxiety disorders. Patient and clinician resources for further information on mindfulness and MBCT are provided.

Predictors of health functioning in two high-risk groups of smokers.

The relative and combined health effects of cigarette smoking, heroin use, and depression were examined in 322 clinically depressed smokers and 117 opioid-dependent smokers participating in two studies of the San Francisco Treatment Research Center. Opioid-dependent smokers averaged 16 years (S.D.=9) of heroin use; 3% of depressed smokers used opiates in the past 6 months. Cigarettes per day (M=15, S.D.=10) and Beck Depression (BDI-II) scores (M=21, S.D.=11) were comparable between the two groups. Health functioning was assessed using the Medical Outcomes Study Short Form (SF-36). Adjusting for demographic differences, depressed smokers reported better physical but poorer emotional health relative to opioid-dependent smokers. Both groups scored significantly lower than published norms (p<.05). Within groups, severity of depressive symptoms, tobacco use, and opiate use were independent predictors of lower health functioning (p<.05). Examining risk-related subgroups based on depression scores (BDI-II> or =20), cigarettes per day (> or =1 pack), and opiate use, number of risk factors was monotonically related to health functioning in both samples. Individuals with two or more risk factors scored the lowest (p<.05). Severity of depressive symptoms, tobacco use, and opiate use contributed individually and collectively to lower health functioning. Blended treatments that target multiple risk factors are needed to improve health outcomes.

A Preliminary Study: Efficacy of Mindfulness-Based Cognitive Therapy versus Sertraline as First-line Treatments for Major Depressive Disorder.

Major depressive disorder (MDD) is the leading cause of disability in the developed world, yet broadly effective treatments remain elusive. The primary aim of this pilot study was to investigate the efficacy of Mindfulness-Based Cognitive Therapy (MBCT) monotherapy, compared to sertraline monotherapy, for patients with acute MDD. This open-label, nonrandomized controlled trial examined a MBCT cohort (N=23) recruited to match the gender, age, and depression severity of a depressed control group (N=20) that completed 8 weeks of monotherapy with the antidepressant sertraline. The 17-item clinician-rated Hamilton Depression Severity Rating Scale (HAMD-17) was the primary outcome measure of depression to assess overall change after 8 weeks and rates of response and remission. The 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR16) was the secondary outcome measure to further assess depression severity. Both cohorts were demographically similar and showed significant improvement in depression ratings. No difference was found in the degree of change in HAMD-17 scores (t(34) = 1.42, p = .165) between groups. Secondary analysis showed statistically significant differences in mean scores of the QIDS-SR16 (t (32) = 4.39, p < 0.0001), with the MCBT group showing greater mean improvement. This study was limited by the small sample size and non-randomized, non-blinded design. Preliminary findings suggest that an 8-week course of MBCT monotherapy may be effective in treating MDD and a viable alternative to antidepressant medication. Greater changes in the self-rated QIDS-SR16 for the MBCT cohort raise the possibility that patients derive additional subjective benefit from enhanced self-efficacy skills.

Depressed smokers and stage of change: implications for treatment interventions.

Tobacco Dependence among smokers with psychiatric disorders has been under-addressed by the mental health, addictions, and tobacco control communities. This study examined depressed smokers' readiness to quit and the applicability of the Stages of Change framework to a psychiatric sample. Currently depressed smokers (N=322) were recruited from four outpatient psychiatric clinics. Participants averaged 16 cigarettes per day (S.D.=10) and 24 years (S.D.=13) of smoking. The majority (79%) reported intention to quit smoking with 24% ready to take action in the next 30 days. Individuals in the preparation stage reported more prior quit attempts, a greater commitment to abstinence, increased recognition of the cons of smoking, and greater use of the processes of change. Precontemplators were least likely to identify a goal related to their smoking behavior. Depressive symptom severity and history of recurrent depressive episodes were unrelated to readiness to quit. This study is one of the first to examine the smoking behaviors of currently depressed psychiatric outpatients. The level and longevity of their tobacco use underscore the need for cessation interventions. The consistency in hypothesized patterns among theoretical constructs of the Stages of Change model supports the transfer of stage-tailored interventions to this clinical population.

Factitious disorders in civil litigation: twenty cases illustrating the spectrum of abnormal illness-affirming behavior.

Physical symptoms are commonly alleged in civil litigation. In some instances these symptoms are originally produced by psychological factors and antedate the alleged injury being claimed as a tort. These cases reflect abnormal illness-affirming behavior. Factitious physical disorders represent a special category of these individuals because they produce their signs and symptoms consciously. This article reviews common features of 20 cases of factitious disorder in which the patients were involved in civil litigation. Attention to these factors can facilitate differential diagnosis, which can lead to improved understanding of causation and appropriate clinical interventions. The authors discuss how the actions of such individuals often shift along the entire spectrum of abnormal illness-affirming behavior over time.

Psychiatric and behavioral correlates of factitious blindness.

In factitious disorder, an individual feigns, exaggerates, or actually self-induces physical or psychiatric illness to achieve ends such as mobilizing care and concern, ventilating aggression, diminishing guilty feelings, or gratifying dependency wishes. We present 2 new cases of factitious binocular blindness, which has rarely been reported but readily illustrates the dramatic range of factitious illness behaviors. Psychiatric and behavioral correlates culled from these cases include extravagant claims about the impairment and ludicrous claims for nonvisual sensory abilities. These patients typically refuse psychiatric care, but earlier detection can help abort the illness deceptions and forestall iatrogenic complications.

Factitious disorders: potential litigation risks for plastic surgeons.

Patients with factitious physical disorders can present with a myriad of signs and symptoms. Common presentations include persistent wounds and abscesses that are often treated by plastic surgeons. Because these individuals are surreptitiously trying to maintain their illness, rather than recover, adverse outcomes are common, particularly when the plastic surgeon has not detected the factitious etiology. Well-meaning plastic surgeons trying to help difficult-to-treat patients may be at high risk for poor outcomes with factitious disorder patients. When these outcomes occur, these patients may focus their underlying anger or other feelings on their plastic surgeons and may initiate litigation. This article discusses 2 cases in which plastic surgeons were sued for malpractice by factitious disorder patients. We outline clues to the recognition of factitious disorders and steps the plastic surgeon can take to initiate appropriate treatment, which may reduce the risk of litigation.

Addressing nicotine dependence in psychodynamic psychotherapy: perspectives from residency training.

OBJECTIVE: According to APA treatment recommendations, psychiatrists should assess and intervene in tobacco use with all of their patients who smoke. The ease with which this occurs may vary by treatment model. This study examined perspectives in residency training to identify a framework for addressing nicotine dependence within psychodynamic psychotherapy. METHOD: The authors collected data from a focus group of psychiatry residents and interviews with psychiatry residency faculty with expertise in psychodynamic psychotherapy. The transcribed interviews were analyzed for key themes and synthesized. RESULTS: Though the residents reported hesitancy to address patients' tobacco use, specifically in psychodynamic psychotherapy, the consensus from the expert faculty consultants was that tobacco interventions can and should be incorporated. The faculty provided suggestions, consistent with a psychodynamic formulation, for assessing patients' tobacco use and their interest in quitting, providing cessation treatment and/or referrals, and following up with patients to address relapse. CONCLUSIONS: The findings provide a useful framework, consistent with a psychodynamic model, for assessing and treating tobacco use with patients. Additional training and supervision likely are needed to increase residents' confidence and comfort with implementing these strategies.

Implementing interpersonal psychotherapy in a psychiatry residency training program.

OBJECTIVE: Interpersonal psychotherapy (IPT) for depression is a brief, well researched treatment for acute major depression. This article describes the implementation of IPT as an evidence-based treatment for depression in a psychiatry residency program. METHOD: The authors tracked the implementation process over 5 years as interpersonal psychotherapy was systematically incorporated into residency training. RESULTS: The authors outline key ingredients for and challenges to effecting change. CONCLUSIONS: Implementation of interpersonal psychotherapy in psychiatry residency training was a cornerstone for learning evidence-based treatment approaches as well as for conveying core psychotherapy concepts.

Management of psychiatric problems in critically ill patients.

Critical care units have become essential elements in modern medicine. These units reflect the highest levels of scientific and technological advance in medicine. Within these units, however, lie significant psychiatric challenges for patients and staff. This article examines the identification and treatment of the most frequent psychiatric problems facing patients entering critical care units, including delirium, depression and anxiety. These conditions are important to address in order to decrease patient suffering and improve morbidity and mortality. The article also addresses some of the most common staff stressors encountered in working in these units. Managing these stressors makes the critical care unit a place where staff can flourish instead of burning out. Specific techniques may help the staff deal with the complex medical, psychological, and ethical issues found in these units in an empathic, compassionate, and well-balanced manner that allows ongoing work satisfaction.