Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression.

BACKGROUND: Psilocybin is being studied for use in treatment-resistant depression. METHODS: In this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological support. The primary end point was the change from baseline to week 3 in the total score on the Montgomery-Åsberg Depression Rating Scale (MADRS; range, 0 to 60, with higher scores indicating more severe depression). Secondary end points included response at week 3 (≥50% decrease from baseline in the MADRS total score), remission at week 3 (MADRS total score ≤10), and sustained response at 12 weeks (meeting response criteria at week 3 and all subsequent visits). RESULTS: A total of 79 participants were in the 25-mg group, 75 in the 10-mg group, and 79 in the 1-mg group. The mean MADRS total score at baseline was 32 or 33 in each group. Least-squares mean changes from baseline to week 3 in the score were -12.0 for 25 mg, -7.9 for 10 mg, and -5.4 for 1 mg; the difference between the 25-mg group and 1-mg group was -6.6 (95% confidence interval [CI], -10.2 to -2.9; P<0.001) and between the 10-mg group and 1-mg group was -2.5 (95% CI, -6.2 to 1.2; P = 0.18). In the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results. Adverse events occurred in 179 of 233 participants (77%) and included headache, nausea, and dizziness. Suicidal ideation or behavior or self-injury occurred in all dose groups. CONCLUSIONS: In this phase 2 trial involving participants with treatment-resistant depression, psilocybin at a single dose of 25 mg, but not 10 mg, reduced depression scores significantly more than a 1-mg dose over a period of 3 weeks but was associated with adverse effects. Larger and longer trials, including comparison with existing treatments, are required to determine the efficacy and safety of psilocybin for this disorder. (Funded by COMPASS Pathfinder; EudraCT number, 2017-003288-36; ClinicalTrials.gov number, NCT03775200.).

Four-week intranasal oxytocin administration reduces attachment avoidance in older women.

The neuropeptide oxytocin (OT) serves as a critical modulator of social cognition and social behavior. Adult attachment is an affiliative process crucial for social interaction across adulthood. Insecure adult attachment comprises two broad dimensions, attachment anxiety and attachment avoidance. Both these dimensions of attachment are currently understudied regarding OT modulation, and especially in older adults. The present study determined the effects of chronic intranasal OT administration on adult attachment in generally healthy older women and men (aged 55-95 years). Embedded in a larger project, participants were randomly assigned to self-administer 24 international units of either OT or a placebo (P) intranasally twice daily for four weeks. The Experiences in Close Relationships Scale assessed adult attachment (anxiety and avoidance) pre- and post-treatment. There was no significant pre- to post-treatment change in attachment avoidance overall, but the treatment x timepoint x sex interaction was significant, in that women (but not men) in the OT (vs. P) group reported decreased attachment avoidance. No comparable effects were observed for attachment anxiety. Results suggest that older women may benefit from chronic intranasal OT treatment by experiencing less attachment avoidance in their adult relationships.

Intranasal oxytocin modulates the salience network in aging.

Growing evidence supports a role of the neuropeptide oxytocin in promoting social cognition and prosocial behavior, possibly via modulation of the salience of social information. The effect of intranasal oxytocin administration on the salience network, however, is not well understood, including in the aging brain. To address this research gap, 42 young (22.52 ± 3.02 years; 24 in the oxytocin group) and 43 older (71.12 ± 5.25 years; 21 in the oxytocin group) participants were randomized to either self-administer intranasal oxytocin or placebo prior to resting-state functional imaging. The salience network was identified using independent component analysis (ICA). Independent t-tests showed that individuals in the oxytocin compared to the placebo group had lower within-network resting-state functional connectivity, both for left amygdala (MNI coordinates: x = -18, y = 0, z = -15; corrected p < 0.05) within a more ventral salience network and for right insula (MNI coordinates: x = 39, y = 6, z = -6; corrected p < 0.05) within a more dorsal salience network. Age moderation analysis furthermore demonstrated that the oxytocin-reduced functional connectivity between the ventral salience network and the left amygdala was only present in older participants. These findings suggest a modulatory role of exogenous oxytocin on resting-state functional connectivity within the salience network and support age-differential effects of acute intranasal oxytocin administration on this network.

Breaking Sad: Unleashing the Breakthrough Potential of Ketamine's Rapid Antidepressant Effects.

Preclinical Research The surprising results of a small clinical trial on the effects of low dose ketamine, a 65-year old anesthetic drug that is also used off-label for chronic pain and recreationally as a club drug, in eight depressed subjects unleashed the most significant advance in antidepressant drug development in decades. That study and subsequent ones have demonstrated that low dose, infused ketamine is able to induce a remission of depression in patients who have failed conventional medications, within 24 h. The apparent increased efficacy and rapid onset of effect of ketamine distinguish it from all other current antidepressant treatments. However, a single infusion of subanesthetic doses of ketamine produces benefits that typically last <3 weeks. The infusions are associated with a transient "psychedelic" experience and increased blood pressure that requires monitoring. There is also a theoretical potential to induce ketamine addiction. These features limit ketamine's ability to be a widely used treatment for depression and thus limit is ability to have a meaningful impact on the heavy morbidity and mortality associated with this disorder, despite its "breakthrough" rate of efficacy and speed of action. While growing numbers of clinicians are using ketamine to treat treatment resistant depression, many in the depression field believe that the aforementioned limiting aspects need to be separated from its remarkable therapeutic effects in order to unlock the breakthrough potential of this agent. To that end, drug development efforts have focused on various features of ketamine as targets for optimization including its modulation of the NMDA receptor, its pharmacokinetics, its chirality and its active metabolites including HNK (2R, 6R)-hyroxynorketamine. Drug Dev Res 77 : 489-494, 2016. © 2016 Wiley Periodicals, Inc.

Intranasal oxytocin administration prior to exposure therapy for arachnophobia impedes treatment response.

BACKGROUND: Recent years have seen the emergence of a new paradigm for treatment of anxiety disorders focusing on development of drugs that facilitate psychotherapies via targeted effects on neuroplasticity. One compound that has generated interest in this regard is oxytocin (OT), a mammalian neuropeptide that modulates activity of the neurocircuit mediating fear extinction and memory processes. Recent research in healthy humans has suggested that intranasal OT administered prior to fear extinction training enhances fear extinction performance, supporting its potential to augment exposure-based psychotherapy. Here, we tested the hypothesis that OT treatment would facilitate response to exposure therapy in patients with specific phobia. METHODS: We conducted a small proof-of-concept trial investigating the effect of pretreatment intranasal OT administration on a brief, single-session exposure treatment for arachnophobia (fear of spiders). The study was randomized, double-blind, and placebo controlled (n = 13 placebo, 11 females; n = 10 OT, 8 females) with 1-week and 1-month follow-up assessments. Dependent measures attended to arachnophobia symptoms (self-report), phobic behavior (behavioral avoidance of spider task), and treatment credibility/therapeutic alliance. RESULTS: Administration of OT prior to exposure therapy tended to impede treatment response as measured by self-report of symptoms at both follow-up periods. OT treatment did not significantly affect behavioral measures of fear. Immediately after OT administration but before therapy, the OT group trended toward less confidence in the treatment. The OT group also trended toward lower ratings of therapeutic alliance than placebo. CONCLUSIONS: These results suggest that OT administration effects on extinction may vary depending on conditions and population.

Effects of chronic intranasal oxytocin on visual attention to faces vs. natural scenes in older adults.

Aging is associated with changes in face processing, including desensitization to face cues like gaze direction and an attentional preference to faces with positive over negative emotional valence. A parallel line of research has shown that acute administration of oxytocin (OT) increases visual attention to social stimuli such as human faces. The current study examined effects of chronic OT administration among older adults on fixation duration to faces that varied in emotional expression, gaze direction, age, and sex. One hundred and twelve generally healthy older adults (aged 55-95 years) underwent a randomized, placebo-controlled, double-blind, between-subject clinical trial in which they self-administered either OT or placebo (P) intranasally twice a day for 4 weeks. The behavioral task involved rating the trustworthiness of faces (i.e., social stimuli) and natural scenes (i.e., non-social control stimuli) during eye tracking and was conducted before and after the intervention. Fixation duration to both the faces and the natural scenes declined from pre- to post-intervention, however this decline was less pronounced among older adults in the OT compared to the P group for faces but not scenes. Further, face cues (emotional expression, gaze direction, age, sex) did not moderate the treatment effect. This study provides first evidence that chronic intranasal OT maintains salience of social cues over time in older adults, perhaps buffering effects of habituation. These findings enhance understanding of OT effects on social cognition among older adults, and would benefit from follow up with a young adult comparison group to directly speak to specificity of observed effects to older adults and reflection of the aging process.

Intramuscular ziprasidone: influence of alcohol and benzodiazepines on vital signs in the emergency setting.

BACKGROUND: Ziprasidone is a second-generation antipsychotic (SGA) approved for agitation. Few previous studies have examined ziprasidone in the emergency department (ED). For instance, it is unknown how often emergency physicians prescribe ziprasidone, whether it is typically prescribed in combination with a benzodiazepine, or whether use of intramuscular (i.m.) ziprasidone and benzodiazepines affects vital signs compared to i.m. ziprasidone alone. OBJECTIVE: Our aims were to determine the demographics of patients receiving ziprasidone in an urban-suburban ED; the relative frequency with which ziprasidone is prescribed; and the effects on vital signs, repeat medication dosage, and lengths of stay. METHODS: This is a multicentered structured chart review from 2003 to 2010 of ziprasidone use at two hospitals. If documented, vital signs were compared in patients who received concurrent benzodiazepines and in those who did not, and in patients who ingested alcohol and in those who did not. RESULTS: Patients on 95 visits received ziprasidone during the study period, with one third of these receiving accompanying benzodiazepines. Forty-nine unique patients who were treated with i.m. ziprasidone had documented vital signs. In these patients, alcohol intoxication was associated with decreased oxygen saturations irrespective of benzodiazepines. Concurrent benzodiazepines had no other deleterious effect on vital signs but resulted in longer ED stays. CONCLUSIONS: This study suggests that many ED physicians, who commonly prescribe a benzodiazepine with a first-generation antipsychotic like haloperidol, have transferred this practice to SGAs like ziprasidone. In this sample, this pairing did not adversely affect vital signs but was associated with marginally longer ED stays. Caution should be exercised when treating alcohol-intoxicated patients with ziprasidone, as this can decrease oxygen saturations.

Pursuing personalized medicine for depression by targeting the lateral or medial prefrontal cortex with Deep TMS.

BACKGROUNDMajor depressive disorder (MDD) can benefit from novel interventions and personalization. Deep transcranial magnetic stimulation (Deep TMS) targeting the lateral prefrontal cortex (LPFC) using the H1 coil was FDA cleared for treatment of MDD. However, recent preliminary data indicate that targeting the medial prefrontal cortex (MPFC) using the H7 coil might induce outcomes that are as good or even better. Here, we explored whether Deep TMS targeting the MPFC is noninferior to targeting the LPFC and whether electrophysiological or clinical markers for patient selection can be identified.METHODSThe present prospective, multicenter, randomized study enrolled 169 patients with MDD for whom antidepressants failed in the current episode. Patients were randomized to receive 24 Deep TMS sessions over 6 weeks, using either the H1 coil or the H7 coil. The primary efficacy endpoint was the change from baseline to week 6 in Hamilton Depression Rating Scale scores.RESULTSClinical efficacy and safety profiles were similar and not significantly different between groups, with response rates of 60.9% for the H1 coil and 64.2% for the H7 coil. Moreover, brain activity measured by EEG during the first treatment session correlated with clinical outcomes in a coil-specific manner, and a cluster of baseline clinical symptoms was found to potentially distinguish between patients who can benefit from each Deep TMS target.CONCLUSIONThis study provides a treatment option for MDD, using the H7 coil, and initial guidance to differentiate between patients likely to respond to LPFC versus MPFC stimulation targets, which require further validation studies.TRIAL REGISTRATIONClinicalTrials.gov NCT03012724.FUNDINGBrainsWay Ltd.

Psilocybin for treatment resistant depression in patients taking a concomitant SSRI medication.

Psilocybin is being investigated as a treatment in adults with treatment-resistant depression (TRD). Withdrawal from serotonergic antidepressant drugs is a common prerequisite for taking part in trials of psilocybin due to the possibility of ongoing antidepressant drugs altering the psychedelic effect. This phase II, exploratory, international, fixed-dose, open-label study explored the safety, tolerability, and efficacy of a synthetic form of psilocybin (investigational drug COMP360) adjunct to a selective serotonin reuptake inhibitor in participants with TRD. Participants received a single 25 mg dose of psilocybin alongside psychological support and were followed-up for 3 weeks. The primary efficacy end point was change in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score from Baseline at Week 3. Secondary end points were safety, including treatment-emergent adverse events (TEAEs), the proportion of responders and remitters at Week 3, and the change from Baseline to Week 3 in Clinical Global Impression-Severity (CGI-S) score. Nineteen participants were dosed and the mean Baseline MADRS total score was 31.7 (SD = 5.77). Twelve (63.2%) participants had a TEAE, most of which were mild and resolved on the day of onset. There were no serious TEAEs or indication of increased suicidal ideation or behavior. At Week 3, mean change from Baseline in MADRS total score was -14.9 (95% CI, -20.7 to -9.2), and -1.3 (SD = 1.29) in the CGI-S. Both response and remission were evident in 8 (42.1%) participants. Larger, comparator-controlled trials are necessary to understand if this paradigm can optimize treatment-outcome where antidepressant drug withdrawal would be problematic.

Single-dose psilocybin for a treatment-resistant episode of major depression: Impact on patient-reported depression severity, anxiety, function, and quality of life.

BACKGROUND: COMP360 is a proprietary, synthetic formulation of psilocybin being developed for treatment-resistant depression (TRD), a burdensome, life-threatening illness with high global impact. Here, we expand upon the previous report of primary outcomes from a phase 2 study of COMP360 in individuals with TRD-the largest randomised controlled clinical trial of psilocybin-to discuss findings of the exploratory efficacy endpoints. METHODS: In this phase 2, double-blind trial, 233 participants with TRD were randomised to receive a single dose of psilocybin 25 mg, 10 mg, or 1 mg (control), administered alongside psychological support from trained therapists. Efficacy measures assessed patient-reported depression severity, anxiety, positive and negative affect, functioning and associated disability, quality of life, and cognitive function. RESULTS: At Week 3, psilocybin 25 mg, compared with 1 mg, was associated with greater improvements from Baseline total scores in all measures. The 10 mg dose produced smaller effects across these measures. LIMITATIONS: Interpretation of this trial is limited by the absence of an active comparator and the possibility of functional unblinding in participants who received a low dose of psilocybin. CONCLUSIONS: Three weeks after dosing, psilocybin 25 mg and, to a lesser degree, 10 mg improved measures of patient-reported depression severity, anxiety, affect, and functioning. These results extend the primary findings from the largest randomised clinical trial of psilocybin for TRD to examine other outcomes that are of importance to patients.

A naturalistic study of intramuscular haloperidol versus intramuscular olanzapine for the management of acute agitation.

OBJECTIVE: Published research on agitation is limited by the difficulty in generalizing findings from trials using moderately agitated, carefully selected patients treated with single agents. More specifically, there are few comparative studies examining common intramuscular (IM) regimens (ie, haloperidol with or without benzodiazepines) with IM atypical antipsychotics. Therefore, we conducted a retrospective chart review to compare IM olanzapine and haloperidol in a "real-world" population with agitation. METHOD: We performed a retrospective evaluation of charts from 146 consecutive emergency department patients who received either IM haloperidol or IM olanzapine for agitation. We used a clinically oriented proxy marker of efficacy--the necessity for additional medication intervention for agitation (AMI)--as our primary outcome measure. RESULTS: Additional medication intervention for agitation was required by 43% (13/30) patients when haloperidol was given alone and by 18% (13/72) when haloperidol was given with a benzodiazepine. In the case of olanzapine, AMI was required by 29% (6/21) of patients receiving olanzapine alone and by 18% (2/11) of patients given olanzapine plus a benzodiazepine. A significant percentage of patients had clinical characteristics (nonpsychiatric triage complaint, drug/alcohol use, severe agitation) that differ from more selective samples. CONCLUSIONS: Overall, these finding suggest that in a naturalistic emergency department setting, haloperidol monotherapy is less effective--at least in requiring AMI--than olanzapine with or without a benzodiazepine or haloperidol plus a benzodiazepine. Moreover, these later 3 regimens seemed comparable. Prospective studies examining the treatment of real-world agitation, including head-to-head comparisons of the haloperidol-benzodiazepine combination with newer IM antipsychotics, are needed.

Dramatic improvement in sexual function induced by intranasal oxytocin.

INTRODUCTION: A variety of sources indicate that oxytocin has beneficial effects on several components of sexuality. This is a case report on a male who had significant, broad-spectrum improvements in sexual function during a course of intranasal oxytocin treatment for social anxiety. AIM: To document a case of diverse, salutary effects of oxytocin on sexual function. METHODS: The patient was in individual treatment for a variety of difficulties, including social avoidance and relational problems. A biopsychosocial evaluation ruled out medical conditions and substance-related issues as a cause of sexual difficulties. After obtaining informed consent, an off-label trial of intranasal oxytocin was administered targeting his social anxiety and relational avoidance. RESULTS: Oxytocin positively impacted a number of components of sexual function, including libido, erection, and orgasm, and was well tolerated. CONCLUSIONS: This is the first case we are aware of documenting broad-spectrum benefits of chronic intranasal oxytocin on male sexual function. Future trials of oxytocin for psychiatric indications should specifically monitor its effects on sexuality, and trials directly investigating oxytocin's impact on aspects of sexual function are warranted.

Potential complications of combining intramuscular olanzapine with benzodiazepines in emergency department patients.

BACKGROUND: Olanzapine (Eli Lilly and Company, Indianapolis, IN) is starting to be used with more frequency in emergency departments (EDs) for agitated patients. The potential complications of the use of olanzapine in combination with a benzodiazepine have not been well characterized in ED patients with undifferentiated agitation. OBJECTIVES: The measurement of vital signs, repeat medication dosage, and ethanol levels in patients who received parenteral (intramuscular [IM]) olanzapine either alone or concurrently with benzodiazepines. METHODS: This is a structured retrospective chart review of all patients who met the criteria of having received IM olanzapine for agitation and having vital signs documented both before medication administration and within 4 h afterwards. RESULTS: Twenty-five patients were identified as meeting the inclusion criteria. Ten patients received olanzapine and benzodiazepine, and 15 patients received olanzapine alone. Regardless of whether or not they received benzodiazepines, patients who had ingested significant amounts of alcohol before arrival in the ED had decreased oxygen saturations after olanzapine administration. Oxygen saturations decreased more in patients who had ingested alcohol and then received olanzapine + benzodiazepines. Two patients (20%) who received olanzapine + benzodiazepines and who had ingested significant amounts of alcohol exhibited hypoxia, defined as lowest O(2) saturation ≤ 92%. CONCLUSIONS: In this relatively small sample, olanzapine plus benzodiazepines seems to be safe in patients who have not ingested alcohol, but may produce potentially significant oxygen desaturations in patients who have. Future, prospective studies should explore the benefits vs. potential risks of adding a benzodiazepine to olanzapine for agitated patients in the ED.

A comparison of the safety of olanzapine and haloperidol in combination with benzodiazepines in emergency department patients with acute agitation.

BACKGROUND: Pharmacologic management of the agitated emergency department patient is controversial. The combination of olanzapine + benzodiazepines is not recommended by the manufacturer, but a recent report suggested harm only if the patient was intoxicated. Whether this is also true for haloperidol + benzodiazepines is not known. OBJECTIVES: The measurement of vital signs and ethanol levels in patients who received haloperidol with or without benzodiazepines was compared to a previous analysis of patients who received olanzapine with or without benzodiazepines. METHODS: This is a structured retrospective chart review of patients who received parenteral haloperidol or parental olanzapine either with or without benzodiazepines. RESULTS: There were 96 patients (71 haloperidol, 25 olanzapine) who met inclusion criteria. No patient in the olanzapine + benzodiazepine group had hypotension, although one patient in the olanzapine-only group did (6.7%); 2 patients in the haloperidol + benzodiazepines group (5.1%) and 2 patients in the haloperidol-only group (6.3%) had hypotension. In alcohol-negative (ETOH-) patients, neither olanzapine alone nor olanzapine + benzodiazepines was associated with decreased oxygen saturations. In ETOH+ patients, olanzapine alone was not associated with decreased oxygen saturations, but olanzapine + benzodiazepines were associated with lower oxygen saturations than haloperidol + benzodiazepines. CONCLUSIONS: In this sample, olanzapine alone or with a benzodiazepine was not associated with more hypotension than haloperidol. However, olanzapine + benzodiazepines were associated with lower oxygen saturations than haloperidol + benzodiazepines in ETOH+ but not ETOH- patients. In patients with known alcohol ingestion, haloperidol, haloperidol + benzodiazepines, or olanzapine alone may be better choices for treatment of agitation.

Age-Related Differences in Amygdala Activation Associated With Face Trustworthiness but No Evidence of Oxytocin Modulation.

The amygdala has been shown to be responsive to face trustworthiness. While older adults typically give higher face trustworthiness ratings than young adults, a direct link between amygdala response and age-related differences in face trustworthiness evaluation has not yet been confirmed. Additionally, there is a possible modulatory role of the neuropeptide oxytocin in face trustworthiness evaluation, but the results are mixed and effects unexplored in aging. To address these research gaps, young, and older adults were randomly assigned to oxytocin or placebo self-administration via a nasal spray before rating faces on trustworthiness while undergoing functional magnetic resonance imaging. There was no overall age-group difference in face trustworthiness ratings, but older compared to young participants gave higher trustworthiness ratings to ambivalently untrustworthy-looking faces. In both age groups, lower face trustworthiness ratings were associated with higher left amygdala activity. A comparable negative linear association was observed in right amygdala but only among young participants. Also, in the right amygdala, lower and higher, compared to moderate, face trustworthiness ratings were associated with greater right amygdala activity (i.e., positive quadratic (U-shaped) association) for both age groups. Neither the behavioral nor the brain effects were modulated by a single dose of intranasal oxytocin administration, however. These results suggest dampened response to faces with lower trustworthiness among older compared to young adults, supporting the notion of reduced sensitivity to cues of untrustworthiness in aging. The findings also extend evidence of an age-related positivity effect to the evaluation of face trustworthiness.

Efficacy and Safety of Deep Transcranial Magnetic Stimulation for Obsessive-Compulsive Disorder: A Prospective Multicenter Randomized Double-Blind Placebo-Controlled Trial.

(Appeared originally in American Journal of Psychiatry 2019; 176:931-938) Reprinted with permission from American Psychiatric Association Publishing.

Rapid acute treatment of agitation in individuals with schizophrenia: multicentre, randomised, placebo-controlled study of inhaled loxapine.

BACKGROUND: There is a need for a rapid-acting, non-injection, acute treatment for agitation. AIMS: To evaluate inhaled loxapine for acute treatment of agitation in schizophrenia. METHOD: This phase III, randomised, double-blind, placebo-controlled, parallel-group study (ClinicalTrials.gov number NCT00628589) enrolled 344 individuals who received one, two or three doses of inhaled loxapine (5 or 10 mg) or a placebo. Lorazepam rescue was permitted after dose two. The primary efficacy end-point was change from baseline in Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) 2 h after dose one. The key secondary end-point was Clinical Global Impression-Improvement scale (CGI-I) score 2 h after dose one. RESULTS: Inhaled loxapine (5 and 10 mg) significantly reduced agitation compared with placebo as assessed by primary and key secondary end-points. Reduced PANSS-EC score was evident 10 min after dose one with both 5 and 10 mg doses. Inhaled loxapine was well tolerated, and the most common adverse events were known effects of loxapine or minor oral effects common with inhaled medications. CONCLUSIONS: Inhaled loxapine provided a rapid, well-tolerated acute treatment for agitation in people with schizophrenia.

Age and intranasal oxytocin effects on trust-related decisions after breach of trust: Behavioral and brain evidence.

Age-related differences in cognition and socioemotional functions, and in associated brain regions, may reduce sensitivity to cues of untrustworthiness, with effects on trust-related decision making and trusting behavior. This study examined age-group differences in brain activity and behavior during a trust game. In this game, participants received "breach-of-trust" feedback after half of the trials. The feedback indicated that only 50% of the monetary investment into their fellow players had resulted in returns. The study also explored the effects of intranasal oxytocin on trust-related decisions in aging, based on suggestions of a modulatory role of oxytocin in response to negative social stimuli and perceptions of trust. Forty-seven younger and 46 older participants self-administered intranasal oxytocin or placebo, in a randomized, double-blind, between-subjects procedure, before they engaged in the trust game while undergoing functional magnetic resonance imaging (fMRI). Younger participants invested less into their game partners after breach-of-trust feedback, while older participants showed no significant difference in their investment after breach-of-trust feedback. Oxytocin did not modulate the behavioral effects. However, after breach-of-trust feedback, older participants in the oxytocin group showed less activity in the left superior temporal gyrus. In contrast, older participants in the placebo group showed more activity in left superior temporal gyrus after breach of trust. The findings may reflect reduced responsiveness to cues of untrustworthiness in older adults. Furthermore, the modulatory effect of oxytocin on left superior temporal gyrus activity among older adults supports the neuropeptide's age-differential role in neural processes in aging, including in the context of trust-related decision making. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Seizure risk with repetitive TMS: Survey results from over a half-million treatment sessions.

BACKGROUND: Seizures are rare during repetitive transcranial magnetic stimulation (rTMS) treatment, but estimating risk is difficult because of study heterogeneity and sampling limitations. Moreover, there are few studies comparing rates between device manufacturers. OBJECTIVE: The objective of this study was to calculate rTMS seizure rates across various FDA-cleared devices in naturalistic clinical settings. METHODS: In July and August 2018, approximately 500 members of the Clinical TMS Society (CTMSS) were electronically surveyed about seizures in their practices. Seizures were distinguished from non-seizures by a remote semi-structured interview with a Board-certified neurologist and Co-Chair of the CTMSS Standards Committee. Exact Poisson calculations were used to estimate seizure rates and confidence intervals across the four most widely used manufacturers. RESULTS: The survey was completed by 134 members, with 9 responses excluded because of data inconsistencies. In total, 18 seizures were reported in 586,656 sessions and 25,526 patients across all device manufacturers. The overall seizure rate was 0.31 (95% CI: 0.18, 0.48) per 10,000 sessions, and 0.71 (95% CI: 0.42, 1.11) per 1000 patients. The Brainsway H-coil seizure rate of 5.56 per 1000 patients (95% CI: 2.77,9.95) was significantly higher (p < 0.001) than the three most widely used figure- 8 coil devices' combined seizure rate of 0.14 per 1000 patients (95% CI: 0.01, 0.51). CONCLUSION: The absolute risk of a seizure with rTMS is low, but generic Brainsway H-coil treatment appears to be associated with a higher relative risk than generic figure- 8 coil treatment. Well-designed prospective studies are warranted to further investigate this risk.

A longitudinal case series of IM ketamine for patients with severe and enduring eating disorders and comorbid treatment-resistant depression.

Severe and enduring eating disorders (EDs) have the highest mortality rate of all psychiatric illnesses (Arch Gen Psychiatry, 2011, 68, 724), especially when comorbid with treatment-resistant depression (TRD) (Psychiatr Res, 2016, 244, 45). We report on four patients with enduring EDs and TRD treated with repeat ketamine over 12 + months, showing improvement in depression with only modest changes in ED symptoms.