Rapid Improvement Of Depressive Symptoms Research Articles

Impact of a private sector residential early parenting program on clinically significant postnatal depressive symptoms experienced by women: Audit of routinely collected data.

Early parenting services in Australia offer brief structured residential programs to address moderate to severe non-psychotic mental health problems among women and unsettled infant/toddler behaviours. The aims were to (1) estimate the immediate and medium-term impact of a five-night psychoeducational residential early parenting program on postpartum depressive symptoms and (2) identify the factors associated with improvement or worsening of postpartum depressive symptoms after completing the program and six weeks post-discharge. Audit of routinely collected medical record data from pre-admission, pre-discharge and post-discharge assessments of a consecutive cohort of women admitted, with their infants/toddlers in a 15-month period to Masada Private Hospital Early Parenting Centre. Data included structured questions assessing: demographic characteristics, access to family and social support, past and current mental health problems, reproductive and obstetric health, chronic health conditions, breastfeeding problems, coincidental major life events, health risk behaviours and infant/toddler feeding, sleeping and crying behaviours. Standardised instruments included the Partner Interaction after Birth Scale (PIBS), the MacLean Screening Instrument for Borderline Personality Disorder (MSI-BPD), Modified Fatigue Assessment Scale (FAS) and selected items from the Karitane Parenting Confidence Scale. The primary outcomes were Edinburgh Postnatal Depression Scale scores at pre-discharge and follow up assessments. Data were analysed using multinomial logistic regression models in which individual and psychosocial characteristics at pre-admission were included as predictors of the likelihood of the changes of the outcomes from pre-admission to pre-discharge and follow up. Complete data from 1220 of 1290 (95%) eligible women were available to assess pre-admission to pre-discharge and from 559 (45.8%) to assess pre-discharge to six-week follow-up changes. The mean pre-admission EPDS score was 11.7 (95% CI: 11.5; 12.0), pre-discharge it was 7.1 (95% CI: 6.9; 7.4) and at six-week follow up it was 5.7 (95% CI: 5.3; 6.1). We found that almost all women experienced a clinically meaningful and rapid improvement in depressive symptoms of at least this magnitude (reduction in mean EPDS scores of 4.6 points from pre-admission to pre-discharge (five nights) and a further reduction of 1.2 points pre-discharge to follow up) (six weeks) and we identified an interpretable set of risk factors for symptoms that did not improve or worsened. The adverse outcomes were associated with having symptoms of borderline personality disorder, a partner experienced as lacking kindness and care, coincidental adverse events and having a child younger than six months. Residential early parenting programs, which take a psycho-educational approach to strengthening caregiving skills, maximising agency, and reducing helplessness, have a rapid beneficial effect on women's postpartum depressive symptoms. These programs provide a valuable and effective component of comprehensive mental health services. Long-term dialectical behaviour therapy is indicated for women with borderline personality disorder traits for whom early parenting programs alone are insufficient to improve depressive symptoms.

Efficacy and safety of zuranolone co-initiated with an antidepressant in adults with major depressive disorder: results from the phase 3 CORAL study

Major depressive disorder (MDD) is a mental health disorder that can cause disability and functional impairment that standard-of-care (SOC) antidepressant therapies (ADTs) can take weeks to treat. Zuranolone is a neuroactive steroid and positive allosteric modulator of synaptic and extrasynaptic γ-aminobutyric acid (GABA) type A receptors approved as an oral, once-daily, 14-day treatment course in adults with postpartum depression and under investigation in adults with MDD. The phase 3 CORAL Study (NCT04476030) evaluated the efficacy and safety of zuranolone 50 mg co-initiated with SOC ADT (zuranolone+ADT) vs placebo co-initiated with SOC ADT (placebo+ADT) in adults with MDD. Patients were randomized 1:1 to once-daily, blinded zuranolone+ADT or placebo+ADT for 14 days, then continued open-label SOC ADT for 28 more days. The primary endpoint was change from baseline (CFB) in the 17-item Hamilton Rating Scale for Depression (HAMD-17) total score at Day 3. Among 425 patients in the full analysis set, CFB in HAMD-17 total score at Day 3 was significantly improved with zuranolone+ADT vs placebo+ADT (least squares mean [standard error], −8.9 [0.39] vs −7.0 [0.38]; p = 0.0004). The majority of patients receiving zuranolone+ADT that experienced treatment-emergent adverse events (TEAEs) reported mild or moderate events. The most common TEAEs present in ≥10% of patients in either zuranolone+ADT or placebo+ADT groups were somnolence, dizziness, headache, and nausea. These results demonstrate that zuranolone+ADT provided more rapid improvement in depressive symptoms compared with placebo+ADT in patients with MDD, with a safety profile consistent with previous studies. Clinical trial registration: ClinicalTrials.gov identifier: NCT04476030.

The development of psilocybin therapy for treatment-resistant depression: an update.

Psilocybin is a classic psychedelic drug that has attracted increasing research interest over the past 10 years as a possible treatment for mood, anxiety and related conditions. Initial phase 2 clinical trials of psilocybin given alongside psychological support for major depression and treatment-resistant depression (TRD) demonstrated encouraging signs of basic safety, further confirmed by a large study in groups of healthy volunteers. The first international multi-centre randomised controlled trial was published in 2022, with signs of efficacy for the 25 mg dose condition in people with TRD when compared with an active placebo. Phase 3 trials in TRD are scheduled to start in 2023. Early evidence suggests that single doses of psilocybin given with psychological support induce rapid improvement in depressive symptoms that endure for some weeks. We therefore provide a timely update to psychiatrists on what psilocybin therapy is, what it is not, and the current state of the evidence-base.

Repeated doses of subcutaneous esketamine in patients with treatment-resistant depression: Case series in a general hospital in Southern Brazil

The use of esketamine appears to be a promising alternative, with rapid improvement in depressive symptoms and suicidal ideation. This study aimed to describe the benefits of subcutaneous (SC) esketamine in patients with treatment-resistant depression. The patients in this study were between 22 and 60 years of age, were diagnosed with treatment-resistant depression, and received SC esketamine. This study highlights that repeated esketamine doses may be a promising treatment option for patients with treatment-resistant depression. Eight of the nine patients met th e criteria for response to depressive symptoms at the end of the treatment period, as evaluated using the HAMD-17 scale. In addition, a reduction in suicidal ideation was observed in patients with depression according to item 9 of the HAM-D17 and item 3 of the PHQ-9. Adverse reactions were mild and transient, with no persistent complications. Thus, SC esketamine may be a safe and beneficial alternative for the treatment of resistant depression and suicidal ideation and/or behavior. The use of the SC route is shown to be possible, mainly because of its ease of use and cost reduction in both equipment and human resources.

Importance of achieving rapid treatment response in major depressive disorder.

Major depressive disorder (MDD) is a leading contributor to disability worldwide and is associated with increased morbidity and mortality. Current pharmacologic treatment options may be ineffective for some patients and can pose several limitations and challenges, including suboptimal response and slow onset of action. Many of these therapies can take 6 to 8 weeks for patients to achieve response and 12 weeks or longer to demonstrate full clinical benefit. Delays in depressive symptom resolution are associated with poor symptomatic and functional outcomes, decreased quality of life, and increased burden on the healthcare system. Achieving response and remission of symptoms soon after diagnosis and treatment is associated with lower rates of relapse and a greater likelihood of functional recovery. An unmet need exists for innovative treatments that offer rapid and sustained effects. This editorial discusses the benefits of rapid improvement in depressive symptoms with available and investigational agents for patients with MDD.

Peripheral proteomic changes after electroconvulsive seizures in a rodent model of non-response to chronic fluoxetine.

Major depressive disorder (MDD) is the psychiatric disorder with the highest prevalence in the world. Pharmacological antidepressant treatment (AD), such as selective serotonin reuptake inhibitors [SSRI, i.e., fluoxetine (Flx)] is the first line of treatment for MDD. Despite its efficacy, lack of AD response occurs in numerous patients characterizing Difficult-to-treat Depression. ElectroConvulsive Therapy (ECT) is a highly effective treatment inducing rapid improvement in depressive symptoms and high remission rates of ∼50-63% in patients with pharmaco-resistant depression. Nevertheless, the need to develop reliable treatment response predictors to guide personalized AD strategies and supplement clinical observation is becoming a pressing clinical objective. Here, we propose to establish a proteomic peripheral biomarkers signature of ECT response in an anxio/depressive animal model of non-response to AD. Using an emotionality score based on the analysis complementary behavioral tests of anxiety/depression (Elevated Plus Maze, Novelty Suppressed Feeding, Splash Test), we showed that a 4-week corticosterone treatment (35μg/ml, Cort model) in C57BL/6JRj male mice induced an anxiety/depressive-like behavior. A 28-day chronic fluoxetine treatment (Flx, 18mg/kg/day) reduced corticosterone-induced increase in emotional behavior. A 50% decrease in emotionality score threshold before and after Flx, was used to separate Flx-responding mice (Flx-R, n = 18), or Flx non-responder mice (Flx-NR, n = 7). Then, Flx-NR mice received seven sessions of electroconvulsive seizure (ECS, equivalent to ECT in humans) and blood was collected before and after ECS treatment. Chronic ECS normalized the elevated emotionality observed in Flx-NR mice. Then, proteins were extracted from peripheral blood mononuclear cells (PBMCs) and isolated for proteomic analysis using a high-resolution MS Orbitrap. Data are available via ProteomeXchange with identifier PXD037392. The proteomic analysis revealed a signature of 33 peripheral proteins associated with response to ECS (7 down and 26 upregulated). These proteins were previously associated with mental disorders and involved in regulating pathways which participate to the depressive disorder etiology.

Effect of brexanolone on depressive symptoms, anxiety, and insomnia in women with postpartum depression: Pooled analyses from 3 double-blind, randomized, placebo-controlled clinical trials in the HUMMINGBIRD clinical program

BackgroundBrexanolone is currently the only treatment specifically approved for postpartum depression (PPD) in the United States, based on the results from one Phase 2 and two Phase 3 double-blind, randomized, controlled trials in the HUMMINGBIRD program. MethodsAdults with PPD randomized to a 60-h infusion of brexanolone 90 μg/kg/h (BRX90) or placebo from the 3 trials were included in these post hoc analyses. Data on change from baseline (CFB) in the 17-item Hamilton Rating Scale for Depression (HAMD-17) total score, HAMD-17 Anxiety/Somatization and Insomnia subscales, and Clinical Global Impression of Improvement (CGI-I) scale were pooled. Response rates for HAMD-17 (≥50 % reduction from baseline) and CGI-I (score of 1 or 2) scales and time to response were analyzed. ResultsPatients receiving BRX90 (n = 102) versus placebo (n = 107) achieved a more rapid HAMD-17 response (median, 24 vs 36 h; p = 0.0265), with an Hour-60 cumulative response rate of 81.4 % versus 67.3 %; results were similar for time to CGI-I response (median, 24 vs 36 h; p = 0.0058), with an Hour-60 cumulative response rate of 81.4 % versus 61.7 %. CFB in HAMD-17 Anxiety/Somatization and Insomnia subscales also favored BRX90 versus placebo, starting at Hour 24 through Day 30 (all p < 0.05), and response rates for both subscales were higher with BRX90. LimitationsThe study was not powered to assess exploratory outcomes. ConclusionsBrexanolone was associated with rapid improvement in depressive symptoms and symptoms of anxiety and insomnia compared with placebo in women with PPD. These data continue to support the use of brexanolone to treat adults with PPD.

Pre-treatment Pain Symptoms Influence Antidepressant Response to Ketamine in Depressive Patients.

BackgroundPain strongly coexists with depression. Ketamine has great analgesic and antidepressant effects, acting as a promising role in treating depression with pain. Few studies have evaluated impact of pain symptoms on antidepressant effect of ketamine infusions. Thus, present study investigated whether pain symptoms in individuals with depression moderate response to ketamine.MethodsOne hundred and four individuals with major depressive disorder and bipolar depression received six intravenous infusions of ketamine. The Montgomery–Åsberg Depression Rating Scale (MADRS) was administered at baseline, the next morning after each infusion and 2 weeks (Day 26) after the last infusion. Pain symptoms were collected at baseline using the short-form McGill Pain Questionnaire (SF-MPQ).ResultsThe prevalence of pain in patients with depression was 48.8%. Mix model analyses showed that pre-treatment pain symptoms assessed by each domain of SF-MPQ significantly moderated antidepressant response to six infusions of ketamine from baseline to day 26 (all p < 0.05). Then follow-up simple slopes analyses suggested that all patients across groups showed a significant symptomatic improvement after ketamine infusions (all p < 0.05), and patients with severe pain (across all domains of SF-MPQ) had greater improvement in depressive symptoms than those with mild pain or non-pain (all p < 0.05).ConclusionA significant and rapid improvement in depressive symptoms was observed in patients with depression and pain after ketamine treatment. Ketamine may be a novel and promising antidepressant preferentially for the therapy of depression with severe pain.

The effects of intranasal esketamine on on-road driving performance in patients with major depressive disorder or persistent depressive disorder.

Background:Intranasal esketamine demonstrates rapid improvement of depressive symptoms. However, transient adverse effects (dissociation, sedation and dizziness) may occur, which could impact driving performance.Aims:To evaluate the effects of 84 mg intranasal esketamine on driving performance in unipolar major depressive disorder (MDD) or persistent depressive disorder (PDD) patients.Methods:The study consisted of two parts. Part A was a single-blind, double-dummy, randomized three-period, cross-over study to compare effects of esketamine versus placebo on next morning driving, 18 ± 2 h post-treatment. Alcohol was administered to demonstrate assay sensitivity. In Part B, same-day driving, 6 ± 0.5 hours post-treatment, was assessed during twice weekly esketamine administration for 3 weeks. Twenty-seven patients with mild-to-moderate MDD or PDD without psychotic features completed a 100 km on-the-road driving test on a public highway in normal traffic. The primary outcome was standard deviation of lateral position (SDLP; cm; weaving of car).Results:In Part A, alcohol impaired driving performance compared to placebo: Least-square means (95% CI), p-value for delta SDLP (cm) compared with placebo: (ΔSDLP = + 1.83 (1.03; 2.62), p < 0.001), whereas esketamine did not: (ΔSDLP = −0.23 (−1.04; 0.58), p = 0.572). In Part B, weekly driving tests showed no differences between placebo baseline SDLP and after esketamine administration over 3 weeks: Day 11: (ΔSDLP = −0.96 (−3.72; 1.81), p = 0.493), Day 18: (ΔSDLP = −0.56 (−3.33; 2.20), p = 0.686) and Day 25: (ΔSDLP = −1.05 (−3.82; 1.71), p = 0.451).Conclusions:In this study, esketamine did not impair on-road driving performance the next morning following a single dose, or on same day after repeated administration.

Is peripartum magnesium sulfate associated with a reduction in postpartum depressive symptoms?

The prevention of postpartum depression is an important area of investigation given its association with major maternal and neonatal sequelae, yet few evidence-based treatments to reduce the frequency of postpartum depression are used. Recent data suggest that N-methyl-D-aspartate receptor antagonists may lead to rapid improvement of depressive symptoms lasting up to 2 weeks. We hypothesized that the N-methyl-D-aspartate receptor antagonist magnesium sulfate would elicit antidepressant effects subsequent to its receipt by women receiving peripartum seizure prophylaxis for a hypertensive disorder of pregnancy. This study aimed to compare the frequency of depressive symptoms at 2 weeks and 6 weeks after delivery between women who did and did not receive peripartum magnesium sulfate for a hypertensive disorder of pregnancy. This prospective cohort study included women with a hypertensive disorder of pregnancy at ≥34 weeks' gestation with singleton gestations. Magnesium sulfate for seizure prophylaxis was administered at the obstetrician's discretion. The Quick Inventory of Depressive Symptomatology survey was administered before hospital discharge and again at 2 weeks and 6 weeks after delivery to assess for postpartum depressive symptoms. The primary outcome for this study was the change in Quick Inventory of Depressive Symptomatology score from baseline to 2 weeks after delivery, which was analyzed both continuously and categorically (any symptom worsening vs stability or improvement). Secondary outcomes included the change in Quick Inventory of Depressive Symptomatology score from baseline to 6 weeks after delivery and the proportion of women who experienced an increase in Quick Inventory of Depressive Symptomatology score at 6 weeks after delivery. Of the 342 women enrolled, 39% (n=134) received magnesium sulfate. Compared with women who did not receive magnesium, women who received magnesium had a significantly smaller change in their mean Quick Inventory of Depressive Symptomatology score (0.6±3.4 vs 1.6±3.0; P=.015) and also were less likely to have an increase in Quick Inventory of Depressive Symptomatology score at 2 weeks after delivery (52% vs 67%; P=.022). These differences were not present at 6 weeks after delivery. After controlling for potential confounders, women who received magnesium continued to have a lower odds of having an increased Quick Inventory of Depressive Symptomatology score from baseline at 2 weeks after delivery than women who did not receive magnesium (adjusted odds ratio, 0.88; 95% confidence interval, 0.78-0.98). Peripartum magnesium was associated with less of an exacerbation in depressive symptoms in the immediate postpartum period. Given the implications of postpartum depression on maternal and child health and the lack of existing prophylaxis, randomized trials should examine this novel potential prophylactic therapy.

Rapid Symptom Improvement in Major Depressive Disorder Using Accelerated Repetitive Transcranial Magnetic Stimulation.

ObjectiveRepetitive transcranial magnetic stimulation (rTMS) has contributed to increase in the remission rate for patients with major depressive disorder (MDD). However, current rTMS treatment is practically inconvenient because it requires daily treatment sessions for several weeks. Accelerated rTMS treatment is as efficient and safe for MDD patients as conventional rTMS.MethodsFifty-one patients with MDD participated in this study; they were randomized into accelerated rTMS (n = 21), conventional rTMS (n = 22), and sham-treatment (n = 8) groups. The accelerated and conventional rTMS groups received 15 sessions for 3 days and 3 weeks, respectively. The sham-treatment group received 15 sham rTMS sessions for 3 days. Primary outcome was assessed using self-report and clinician-rated Korean Quick Inventory of Depressive Symptomatology (KQIDS-SR and KQIDS-C, respectively). Adverse effects were monitored using the Frequency, Intensity, and Burden of Side Effects Rating scale. Changes in depressive symptoms were compared among the three groups using mixed model analyses.ResultsFor the KQIDS-SR score, there was a significant main effect of “time” (F3,47 = 11.05, p < 0.001), but no effect of “group” (F2,47 = 2.04, p = 0.142), and a trend-level interaction effect of “group × time” (F6,47 = 2.26, p = 0.053). Improvement in depressive symptoms, based on the KQIDS-SR score 3 weeks after treatment, was more prominent in the accelerated rTMS group than in the sham-treatment group (p = 0.011). Tolerability was comparable among the three groups.ConclusionThe accelerated rTMS treatment group showed rapid improvement of depressive symptoms compared with the sham-treatment and conventional rTMS treatment groups. Therefore, accelerated rTMS treatment could be a viable option for MDD, with improved accessibility.

Effect of green tea consumption in treatment of mild to moderate depression in Iranian patients living with HIV: A double-blind randomized clinical trial

ObjectiveDepression affects people living with HIV (PLWH) compliance leading to poor control infection. Previous observational studies showed an anti-depression effect of green tea extract (GTE). The therapeutic effect of GTE on depression were investigated in PLWH receiving antiretroviral therapy (ART). MethodsFifty PLWH on ART with diagnose of mild to moderate of depression, participated in a double-blind, placebo-controlled trial and underwent 12 weeks of treatment with either 400 mg GTE capsules or placebo twice daily. The Hamilton depression scale of patients was measured before, 6 weeks and 12 weeks after treatment in two groups. The primary outcome measure was performed to evaluate the efficacy of GTE in improving depressive symptoms. ResultsThe mean of Hamilton score showed a significant difference between the two groups after 12 weeks (P = 0.035). Repeated measures ANOVA test showed a significant effect for time × treatment interaction on the Hamilton mean score between the two groups (P = 0.000). ConclusionIt seems the use of GTE capsules in PLWH on ART is safe and could lead to greater and more rapid improvement in depressive symptoms than placebo. Thus it can be considered as an alternative therapy for mild to moderate depression. Further studies with higher sample size and longer follow-up and comparisons with other antidepressive drugs are warranted.

Efficacy of psychedelic treatments on depressive symptoms: A meta-analysis.

Psychedelic drugs have shown an efficacy in some psychiatric disorders and have an original mechanism of action with a 5-HT2A agonism. The aim of this meta-analysis was to assess by a quantitative analysis the putative efficacy of psychedelic drugs on depressive symptoms and to investigate the kinetic of this efficacy. We searched the MEDLINE and PsycINFO databases through April 2019, without limits on year of publication. Means and standard deviations were extracted to calculate standardized mean differences (SMD). Scores of depressive symptoms were compared with baseline scores at days 7, 14, and 21; weeks 4-5 and 6-8; and months 3 and 6. Eight studies were included in this meta-analysis. A significant decrease of depressive symptoms was found from day 1 (n = 5 studies; SMD = ‒1.4, 95% confidence interval (CI): ‒2.33 to ‒0.48, p = 0.003) to 6 months (n = 4 studies; SMD = ‒1.07, 95% CI: ‒1.44 to ‒0.7, p < 0.001) after psychedelic sessions. No serious adverse effect was reported in all included studies. A transient increase of the heart rate, blood systolic, and diastolic pressure were found after psychedelics compared with placebo. This meta-analysis shows that psychedelic treatments were safe and could contribute to a rapid improvement of depressive symptoms.

Esketamine Approved for Refractory Depression

Esketamine Approved for Refractory Depression

Esketamine nasal spray effective for rapid improvement of depressive symptoms

Esketamine nasal spray effective for rapid improvement of depressive symptoms

Esketamine nasal spray effective for rapid improvement of depressive symptoms

Esketamine nasal spray effective for rapid improvement of depressive symptoms

Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study.

The authors compared the efficacy of standard-of-care treatment plus intranasal esketamine or placebo for rapid reduction of symptoms of major depression, including suicidality, among individuals at imminent suicide risk. In a double-blind, multicenter, proof-of-concept study, 68 participants were randomly assigned to receive esketamine (84 mg) or placebo twice weekly for 4 weeks, in addition to comprehensive standard-of-care treatment. The primary efficacy endpoint was change in score from baseline to 4 hours after initial dose on the Montgomery-Åsberg Depression Rating Scale (MADRS). Clinician global judgment of suicide risk (from the Suicide Ideation and Behavior Assessment Tool) was also assessed. Secondary endpoints included these measures at 24 hours and double-blind endpoint at day 25. A significantly greater improvement in MADRS score was observed in the esketamine group compared with the placebo group at 4 hours (least-square mean difference=-5.3, SE=2.10; effect size=0.61) and at ∼24 hours (least-square mean difference=-7.2, SE=2.85; effect size=0.65), but not at day 25 (least-square mean difference=-4.5, SE=3.14; effect size=0.35). Significantly greater improvement was also observed in the esketamine group on the MADRS suicidal thoughts item score at 4 hours (effect size=0.67), but not at 24 hours (effect size=0.35) or at day 25 (effect size=0.29). Between-group reductions in clinician global judgment of suicide risk scores were not statistically different at any time point. The most common adverse events among participants in the esketamine group were nausea, dizziness, dissociation, unpleasant taste, and headache. These preliminary findings indicate that intranasal esketamine compared with placebo, given in addition to comprehensive standard-of-care treatment, may result in significantly rapid improvement in depressive symptoms, including some measures of suicidal ideation, among depressed patients at imminent risk for suicide.

NMDA Antagonists for Treatment-Resistant Depression.

Fifteen to thirty percent of patients with major depressive disorder do not respond to antidepressants that target the monoaminergic systems. NMDA antagonists are currently being actively investigated as a treatment for these patients. Ketamine is the most widely studied of the compounds. A brief infusion of a low dose of this agent produces rapid improvement in depressive symptoms that lasts for several days. The improvement occurs after the agent has produced its well characterized psychotomimetic and cognitive side effects. Multiple infusions of the agent (e.g., 2-3× per week for several weeks) provide relief from depressive symptoms, but the symptoms reoccur once the treatment has been stopped. A 96-h infusion of a higher dose using add-on clonidine to mitigate the psychotomimetic effects appears to also provide relief and resulted in about 40% of the subjects still having a good response 8weeks after the infusion. As this was a pilot study, additional work is needed to confirm and extend this finding. Nitrous oxide also has had positive results. Of the other investigational agents, CERC-301 and rapastinel remain in clinical development. When careful monitoring of neuropsychiatric symptoms has been conducted, these agents all produce similar side effects in the same dose range, indicating that NMDA receptor blockade produces both the wanted and unwanted effects. Research is still needed to determine the appropriate dose, schedule, and ways to mitigate against unwanted side effects of NMDA receptor blockade. These hurdles need to be overcome before ketamine and similar agents can be prescribed routinely to patients.

Deep brain stimulation of the medial forebrain bundle elevates striatal dopamine concentration without affecting spontaneous or reward-induced phasic release

Deep brain stimulation (DBS) of the medial forebrain bundle (MFB) induces rapid improvement of depressive symptoms in patients suffering from treatment-refractory major depressive disorder (MDD). It has been hypothesized that activation of the dopamine (DA) system contributes to this effect. To investigate whether DBS in the MFB affects DA release in the striatum, we combined DBS with fast-scan cyclic voltammetry (FSCV) in freely moving rats. Animals were implanted with a stimulating electrode at the border of the MFB and the ventral tegmental area, and a FSCV microelectrode in the ventromedial striatum to monitor extracellular DA during the acute onset of DBS and subsequent continued stimulation. DBS onset induced a significant increase in extracellular DA concentration in the ventromedial striatum that was sustained for at least 40s. However, continued DBS did not affect amplitude or frequency of so-called spontaneous phasic DA transients, nor phasic DA release in response to the delivery of unexpected food pellets. These findings suggest that effects of DBS in the MFB are mediated by an acute change in extracellular DA concentration, but more research is needed to further explore the potentially sustained duration of this effect. Together, our results provide both support and refinement of the hypothesis that MFB DBS activates the DA system: DBS induces an increase in overall ambient concentration of DA, but spontaneous or reward-associated more rapid, phasic DA dynamics are not enhanced. This knowledge improves our understanding of how DBS affects brain function and may help improve future therapies for depressive symptoms.

Single-Dose Ketamine Associated with Rapid Improvement of Depressive Symptoms

Single-Dose Ketamine Associated with Rapid Improvement of Depressive Symptoms