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Newer antidepressants don’t appear to carry an increased risk of cardiovascular events, according to findings from a British cohort study.
As a class, selective serotonin reuptake inhibitors (SSRIs) didn’t hike the individual risks of arrhythmia, stroke, or MI, Carol Coupland, PhD, of the University of Nottingham in England, and colleagues reported online in The BMJ.

Interestingly, citalopram — which has a boxed warning about QT prolongation — was not associated with arrhythmia, even at high doses. But the researchers acknowledged that the “numbers in this category were relatively small” and that the finding contrasts with studies, including randomized controlled trials, that have found QT interval prolongation in patients on the drug.
Torsades de pointes, the type of arrhythmia most closely related to QT interval prolongation, “is extremely rare, so cohort studies, including ours, cannot rule out an association for this particular type of arrhythmia,” Coupland and colleagues wrote.
Daniel Weintraub, MD, of the University of Pennsylvania, who was not involved in the study, said psychiatrists are aware of the relationship between citalopram and QT interval prolongation, although it’s a “somewhat separate issue” from arrhythmia in general.
Still, the “prolonged QTc data come from prospective data in a clinical trial, with ECG monitoring, so I have no doubt about their validity,” Weintraub told MedPage Today.
And he said that while it’s “hard to draw too many conclusions from these large observational studies … I think our sense is overall that newer antidepressants are safe from a cardiovascular/cerebrovascular standpoint.”

Philip Muskin, MD, of Columbia University Medical Center and a spokesperson for the American Psychiatric Association, agreed that there “aren’t any shocks here.”
“I think there’s reassurance,” Muskin said. “There’s no logic that they should cause MI or embolic stroke,” noting that SSRIs are mild anticoagulants.
Researchers have known that depression is linked to an increased risk of cardiovascular outcomes, but it’s not clear if using antidepressants, particularly SSRIs, increases or decreases that cardiovascular risk.
Only citalopram carries an FDA cardiovascular risk warning, which solely pertains to the prolonged QT interval issue, with a recommendation not to dose more than 40 mg a day.
Coupland and colleagues looked at three cardiovascular outcomes separately — myocardial infarction, stroke or transient ischemic attack (TIA), and arrhythmia — among 238,963 patients ages 20 to 64 from a cohort of general practice patients in the U.K., where the mean age was 40 and 61% were women.

Over 5 years’ follow-up, 772 patients had an MI, 1,106 had a stroke or TIA, and 1,452 had an arrhythmia.
Overall, the researchers found no associations between antidepressant class and risk of heart attack, although in the first year of treatment, those on SSRIs actually had a significantly lower risk of MI compared with not taking SSRIs (aHR 0.58, 95% CI 0.42 to 0.79).
Among individual drugs, fluoxetine was associated with a significantly reduced MI risk (aHR 0.44, 95% CI 0.27 to 0.72) — but the tricyclic antidepressant lofepramine carried a significantly higher MI risk (aHR 3.07, 95% CI 1.50-6.26).
There were no associations between antidepressant class or individual drugs and the risk of stroke or TIA.
In general, antidepressant classes were not tied to risk of arrhythmia — but this risk was increased during the first month of treatment with tricyclic antidepressants (aHR 1.99, 95% CI 1.27-3.13).

Fluoxetine appeared to be protective against arrhythmia (aHR 0.74, 95% CI 0.59 to 0.92), and, interestingly, citalopram was not associated with arrhythmia risk even at high doses.
Weintraub noted that the study “didn’t involve older people, who likely have a different risk profile.”
Muskin agreed that the paper “would have been better” if patients 65 and up were also evaluated, but this “doesn’t take away from the study. You just know that when you extrapolate to the elderly, you have to be more careful.”
The researchers disclosed no financial relationships with industry.

Deep brain stimulation (DBS) may be effective for relieving symptoms in treatment-resistant depression, Dutch researchers reported.
A significant decrease in depressive symptoms was observed in 10 of 25 patients given DBS of the central anterior limb of the internal capsule (vALIC), Isidoor Bergfeld, MSc, of the University of Amsterdam in the Netherlands, and colleagues reported online in JAMA Psychiatry.

The treatment was well-tolerated and elicited a partial response in six additional patients, and remission was achieved in five patients. Importantly, patients receiving sham stimulation experienced significantly more depressive symptoms than during the active treatment phase of the study, the researchers said.
“To our knowledge, this is the first study showing the efficacy of deep brain stimulation of the ventral anterior limb of the internal capsule that cannot be attributed to placebo effects,” they wrote. “Further specification of targets and the most accurate setting optimization as well as larger randomized clinical trials are necessary.”
The study design (an open-label, extended optimization period followed by a blinded, randomized, discontinuation experiment once a stable response was achieved) makes it “most compelling” and points the way to future studies, Helen Mayberg, MD, of Emory University in Atlanta, wrote in an accompanying editorial.
The discriminating effects of active-versus-sham stimulation demonstrated in phase II of the study were not seen in the recent industry-sponsored randomized clinical trial that used the more traditional, up-front active-versus-sham design, she noted.
“With increasing interest in targeted circuit modulation for depression and other psychiatric disorders, [this] study further highlights the need to seriously consider customized trial designs in planning any invasive device trials, be it DBS, vagus nerve stimulation, or a future novel technology,” she wrote.

The study also revealed the risk of a fixed optimization period and provided new insights into how time to stable response can vary between patients treated with vALIC, Mayberg said.
“The implicit instability of the DBS response reported in this study provides new evidence that experimental studies using invasive devices might best be structured so that they are not prematurely terminated at an arbitrary time point,” she wrote. “Such an approach will enable a more complete characterization of the trajectory and timeline of behavioral changes in individual participants prior to initiating large-scale, industry-sponsored trials.”
The open-label trial followed by a double-blind, randomized crossover phase enrolled 25 patients in two hospitals in the Netherlands between March 22, 2010, and May 8, 2014. A final follow-up was conducted on Dec. 19, 2014.
Patients were between 18 and 65 years of age, with a primary diagnosis of major depressive disorder lasting for more than 2 years. Other inclusion criteria included a 17-item Hamilton Depression Rating Scale (HAM-D-17) score of 18 or higher, and a Global Assessment of Function score of 45 or lower.
Eight of the patients were male and the mean age was 53.2 years. All patients received bilateral implants of four contact electrodes through the anterior limb of the internal capsule.

After 3 weeks’ recovery, a psychiatrist or psychologist assessed patients’ responses and adverse events after maintaining standardized optimization of DBS settings for at least 1 week. If there was no clinical improvement or only partial improvement, voltages greater than 6.0 V were tested and pulse width and frequency adjusted.
No psychotherapy was incorporated into the DBS treatment but psychiatrist-ordered medication adjustments — for symptom improvement, for instance — were permitted.
A stable response of at least 4 weeks — or a maximum of 52 weeks of DBS — signaled the end of the optimization period.
Following this, patients immediately entered the randomized, double-blind crossover phase consisting of two 6-week periods of either active or sham DBS.
In the optimization period, the mean HAM-D-17 scores decreased from 22.2 at baseline to 15.9 (P=0.001). Montgomery-Åsberg Depression Rating Scale scores fell from 34.0 to 23.8 (P<0.001) and Inventory of Depressive Symptomatology-Self-report scores went from 49.3 to 38.8 (P=0.005).

A total of 16 patients (nine responders and seven nonresponders) entered the randomized crossover phase. During active DBS, patients scored significantly lower on the HAM-D-17 scale (13.6) than during sham DBS (23.1) (P<0.001).
One patient experienced severe nausea during surgery, four patients attempted suicide, and two patients reported suicidal ideation.
In six patients, the optimization period exceeded the maximum of 52 weeks, and this may have led to a higher response rate, the researchers acknowledged. While two responders had minor changes in antidepressant medication during the optimization phase, “it is unlikely that these minor changes explained the full response.”
During the sham phase, an abrupt symptom increase was seen in 10 patients. Although they were blinded to treatment, they could “accurately predict the stimulation setting,” the researchers wrote.
They emphasized that in future, crossover studies “should consider phases of no more than 1 week to ensure patient safety, with a washout period between phases to minimize possible carryover effects.”

An open-label adaptive design may be the most prudent approach for a high-risk procedure performed in a vulnerable population, Mayberg said, noting that patients with implanted devices continue to receive the experimental therapy after the study has ended.
One of the “unexplored” variables in this study is patient heterogeneity in treatment-resistant depression, she said, suggesting that retrospective analysis of patients who responded well to DBS could be followed by new studies to test these variables prospectively.
Finally, ongoing support for patients with treatment-resistant depression, including additional rehabilitation, must be built into studies of DBS, she emphasized, calling it “an obligation to the patients who engage in these demanding and risky trials.”
This study was supported by Medtronic, which provided the devices, as well as the Netherlands Organisation for Scientific Research/ZonMw.

One of the study authors also disclosed a relationship with Lundbeck.

Mayberg disclosed a consulting agreement with St Jude Medical to develop deep brain stimulation for the treatment of severe depression. She disclosed funding from the Hope for Depression Research Foundation, the National Institute of Mental Health, the National Institutes of Health Loan Repayment Program, and Medtronic.

Growth charting the brain’s networks could provide a novel way to detect neurocognitive abnormalities such as impaired attention functioning in youth, researchers said.
Resting-state functional neuroimaging of a small cohort of youth revealed deviations from normal patterns of brain maturation that predicted the diagnosis of attention-deficit/hyperactivity disorder (ADHD), Chandra Sripada, MD, PhD, of the University of Michigan in Ann Arbor, and colleagues reported online in JAMA Psychiatry.

“We mapped the normative maturational trajectories of major components of the functional connectome and showed that downshifted component expression relative to the normative profile (shallow maturation) is implicated in both impaired attention task performance and ADHD,” they wrote.
“Many psychiatric disorders are thought to have their origins in early neurodevelopmental events,” they added. “Our results invite further investigation into the use of network growth charting to identify patterns of brain dysmaturation that can serve as early, objective markers of cognitive problems and disorder vulnerability.”
The analysis showed that patterns of deviation from normative growth trajectories indicated sustained attention functioning. These patterns were a reliable biomarker of severe attention impairment, expressed as the peak receiver operating characteristic curve measured by area under the curve (79.3%), the researchers reported.
“In particular, a down-shifted pattern of intrinsic connectivity network (ICN) maturation (shallow maturation), rather than a right-shifted pattern (lagged maturation), was implicated in reduced attention performance,” Sripada and colleagues said. “Finally, parallel associations between ICN dysmaturation and diagnosis of attention-deficit/hyperactivity disorder were identified.”
This charting approach revealed the role of ICNs in sustained attention, they said. When individuals deviated from normative trajectories in the development of ICNs, they consistently exhibited worse sustained attention performance.

Other researchers have used functional connectomes — the coordinated patterns of brain activity, measured by functional magnetic resonance imaging — to predict sustained attention performance.
In the study, a total of 519 youths ages 8 to 22 were analyzed out of 1,000 who underwent brain imaging as part of a prospective, population-based sample of 9,498 youths in the Philadelphia Neurodevelopmental Cohort.
All participants had previously undergone genomic testing, neurocognitive assessment, and neuroimaging.
A total of 25 (4.8%) met criteria for attention-deficit/hyperactivity disorder. The mean age of the youth was 15.7 years, and 43% were male.
Data collection took place between Nov. 1, 2009, and Nov. 30, 2011, and data analysis was carried out between Feb. 1, 2015, and Jan. 15, 2016.

The investigators used the data to create maps of functional connectivity called components. The 15 components they identified varied in expression between participants, revealing a signature pattern of functional connectivity between and within brain networks.
By mapping how these components changed over time in the primarily healthy cohort, the researchers were able to create a normative growth curve and calculate how far each component’s expression deviated from age-expected values for a “maturational deviation score.”
This score accounted for approximately 25% of the variance in sustained attention skills, Philip Shaw, BM, BCh, PhD, of the National Human Genome Research Institute, said in an accompanying editorial. By comparison, general intelligence explained about 7% of the variance, he noted.
“The finding represents an impressive validation of how patterns of functional connectivity can pertain to a core cognitive skill,” Shaw wrote. “The question now arises of whether these functional alterations also contribute to the deficits in sustained attention found in other childhood disorders — not just ADHD.”
Since growth is a longitudinal process unique to each child, the cross-sectional data analysis used in this study, while performed “elegantly,” is “inherently limited,” Shaw said, adding that “definitive growth curves will require longitudinal observations.”

The diagnostic usefulness of a test “depends on many factors, but odds ratios in the double digits are usually needed,” he pointed out. And while “the further step to a specific diagnosis is less compelling,” this may not be a major drawback. “The goal of growth charts is not to clinch a specific diagnosis, but rather to prompt and inform further assessment.”
Translation of in vivo measures of the brain’s functional architecture into psychiatric growth charts “will be challenging,” warned Shaw, “but the conceptual and empirical foundations have been laid.”
Funding for this research was provided by the National Institutes of Health, the Center for Computational Medicine, and the John Templeton Foundation.

Shaw is funded by the Intramural Programs of the National Human Genome Research Institute and National Institute of Mental Health.

No conflicts of interest were disclosed.

Mindfulness-based cognitive therapy (MBCT) was effective at reducing risk of relapse in patients with recurrent depression, especially in those with the most severe residual symptoms, a meta-analysis showed.
Patients receiving MBCT had a significantly reduced risk of depressive relapse within a 60-week follow-up period compared with those who received usual care (HR 0.69, 95% CI 0.58-0.82), Willem Kuyken, PhD, of the Warneford Hospital at Oxford University, and colleagues reported online in JAMA Psychiatry.

Patients receiving MBCT had comparable outcomes to those who received other active treatments (HR 0.79, 95% CI 0.64-0.97), they reported.
“While previous research has shown the superiority of MBCT compared with usual care, this study provides important new evidence that MBCT is also effective compared with other active treatments and that its effects are not restricted to particular groups defined by age, educational level, marital status, or sex,” the researchers wrote.
“The finding that MBCT may be most helpful for patients with higher levels of depressive symptoms adds to an emerging consensus that the greater the risk for depressive relapse/recurrence, the more benefit MBCT offers.”
These results both replicate and extend previous work, Kuyken and colleagues said: “We found that MBCT reduces the risk of depressive relapse/recurrence compared with the current mainstay approach, maintenance antidepressants.”
Although MBCT teaches patients at high risk of relapse how to keep depressive symptoms at bay, its protective effect appears to fade over time. In addition, patients whose symptoms were not as severe “appeared to receive less benefit,” they said.

In the study — an update to a previous meta-analysis — individual patient data was compiled from 9 published randomized trials of MBCT in Europe and North America. The data were identified using EMBASE, PubMed/Medline, PsycINFO, Web of Science, Scopus, and the Cochrane Controlled Trials Register, and had been conducted from November 2010 to November 2014.
A total of 1,258 patients were included. Three-quarters were female and the mean age was 47.1 years. Among 1,234 participants, the mean age at onset of depression was 26 years and in 1,200 participants, 694 (57.8%) had 5 or more past depressive episodes.
The analysis demonstrated that there was no statistically significant interaction with MBCT treatment between sociodemographic factors such as age, sex, education, and relationship status or psychiatric variables including age at onset and the number of previous episodes of depression.
The researchers pointed out that a recent meta-analysis comparing the effectiveness of all psychological interventions to prevent recurrence with usual care and antidepressants has suggested that protective effects of MBCT are comparable to cognitive therapy versus usual care and interpersonal therapy versus usual care.
“The meta-analysis by Kuyken et al provides strong evidence that MBCT is effective in reducing risk of depressive relapse and is particularly effective for patients with higher levels of depressive severity before treatment,” Richard Davidson, PhD, founder of the Center for Healthy Minds at the University of Wisconsin-Madison, commented in an accompanying editorial.

Previous studies have indicated that one of the key variables behind the effectiveness of MBCT is how often individuals put it into practice, Davidson noted. “While this type of association is not always present, it is a potentially very important variable and may account for considerable variability across patients and across studies.”
Daily practice logs “can provide useful information with which to correlate changes in clinical and other outcomes,” he added.
Looking ahead, there is an opportunity to take a closer look at which patients benefit most from MBCT, the mechanisms behind its beneficial effect, and how to more effectively measure the mediators of therapeutic change, Davidson said.
“Combining insights and methods from basic cognitive and affective neuroscientific research on mindfulness with future clinical trials provides a framework for addressing these additional questions,” he wrote.
An examination of the synergistic effect of MBCT and “neuroplasticity enhancers” such as physical exercise might also be of interest, he said.

The researchers made a number of recommendations for future trials that relate directly to the limitations of their analysis and which could help “address remaining uncertainties and improve the rigor of the field.”
An active control group should be considered, as well as the use of comparable primary and secondary outcomes such as the Structured Clinical Interview for DSM for depressive relapse, they said. In addition, they recommended that key variables such as race/ethnicity and employment be considered, that follow-up time be lengthened, that steps be taken to ensure generalizability of results, and that data sharing systems be created to systematically record and report adverse events.
The study was supported by the Wellcome Trust, the National Institute for Health Research Healthy Technology Assessment program, the National Institute for Health Research Collaboration for Leadership in Applied Health Research, Care South West Peninsula at the Royal Devon, Exeter National Health Service Foundation Trust, and the Medical Research Council.

Kuyken is director of the Oxford Mindfulness Centre, which was founded by study co-author, Mark Williams, PhD, its director until 2013. Anne Speckens, MD, is founder and clinical director of the Radboud UMC Centre for Mindfulness; and Helen Ma, PhD, is director of the Centre for Mindfulness, Hong Kong. Zindel Segal, PhD, disclosed a relationship with NogginLabs.

Davidson disclosed that his editorial research was funded by the National Center for Complementary and Integrative Health of the National Institutes of Health as well as several gifts to the Center for Healthy Minds, a nonprofit corporation associated with the Center for Healthy Minds at the University of Wisconsin-Madison. Davidson also disclosed that he is founder and president of Healthy Minds Innovations.

More patients with serious psychological distress had insurance coverage following the Affordable Care Act, but that didn’t change whether they’d seen a healthcare professional recently, researchers reported.
In an analysis of data from the National Health Interview Survey (NHIS), the number of uninsured adults ages 18 to 64 fell from 28.1% in 2012 to 19.5% in first 9 months of 2015, Robin Cohen, PhD, and Emily Zammitti, MPH, of the National Center for Health Statistics, reported in a Data Brief.

But there was no change in the proportion of adults with serious psychological distress who had a usual place to go for medical care or who had talked to a healthcare provider in the past year, they reported. These figures hovered just under 80% and just under 90%, respectively.
The findings were worse for mental healthcare specifically — the proportion of distressed adults who had seen a mental health professional in the past year fell during that time, from about 42% to 34%.
“This may be due to a number of factors, such as an increasing trend in obtaining mental health care from primary care providers or an increasing shortage of mental health professionals,” Cohen and Zammitti wrote. “Exploring these hypotheses requires further analysis, using more detail than NHIS provides.”
In this study, serious psychological distress was measured on the Kessler 6 nonspecific distress scale, which asks about the frequency of six symptoms, including nervousness and hopelessness, in the past month. Patients meeting this definition were about 3%-4% of the weighted sample during the analysis period.
The fall in the rate of uninsured in this population corresponded with an increase in private insurance coverage during that time, from 30% to 38%. Rates of public coverage remained relatively constant, they reported.

Cost-related barriers to care appear not to be an explanation for the decline in mental healthcare provision. The researchers found that many measures associated with not receiving care or delaying services due to cost fell during this period for patients with serious psychological distress.
In the first 9 months of 2015, fewer patients said they had forgone mental healthcare because of cost in the past year, and they were more able to afford necessary medical care and prescription drugs at the end of the study period.
Despite these improvements, disparities remain, Cohen and Zammitti wrote.
Although the percentage of uninsured had fallen to 19.5% among this group, this was still half again greater than the 12% of patients without distress who remained uninsured.
And about a quarter of patients with distress still reported being unable to pay for necessary medical care in the last year compared with only about 6% of those without the condition.
“It is possible that improved access does not necessarily lead to a successful treatment for serious psychological distress,” they wrote. “It is also possible that those who still have distress are increasingly those with poor access.”
The researchers disclosed no financial relationships with industry.

WASHINGTON — The atypical antipsychotic drug aripiprazole (Abilify, Abilify Maintena, Aristada) may trigger loss of impulse control, leading to “compulsive or uncontrollable urges to gamble, binge eat, shop, and have sex,” the FDA warned Tuesday.
New warnings will be added to labels and patient medication guides for aripiprazole products.
The FDA noted that compulsive gambling was already included on the products’ labels as a known adverse effect, but event reports submitted to the agency point to a wider variety of impulse-control problems. These are similar to those previously seen with dopamine agonist drugs used in Parkinson’s disease such as pramipexole (Mirapex) and rotigotine (Neupro).
A search of the published literature and the agency’s adverse event database yielded 184 reports of impulse-control problems associated with aripiprazole (167 in U.S. patients). Pathological gambling was the most common, the FDA said, but reports also told of compulsive spending, shopping, and eating, as well as hypersexual behavior.
In most cases, these behaviors had not previously been noted in the patients, and they resolved after stopping the drug.
The FDA did not identify a specific mechanism to account for these effects, but it hinted at one: Aripiprazole is unique among atypical antipsychotics in that, whereas others in the class are strong blockers of dopamine receptors in the central nervous system, aripiprazole is only a partial blocker, the agency said.
Also noted was that the 184 reports spanned the 13-year history of the drug’s availability; in 2015 alone, the agency said, some 1.6 million people filled a prescription for aripiprazole at retail pharmacies.

The FDA recommended that physicians discuss these newly recognized risks with patients and caregivers, and that providers should quiz patients about “any new or increasing urges” while taking the drug.
Aripiprazole products are approved for schizophrenia, bipolar disorder, Tourette syndrome, and irritability in autistic disorders, and for depression in combination with traditional antidepressants.

Repeated infusions of ketamine “rapidly and robustly” decreased chronic thoughts of suicide in half of patients with treatment-resistant depression, secondary analysis from a preliminary open-label study showed.
At the end of the series of infusions, 7 out of 14 patients — even those who were still depressed — had a score of zero on the Columbia-Suicide Severity Rating Scale [C-SSRS] for remission of suicidal ideation, Dawn Ionescu, MD, of Massachusetts General Hospital in Boston, and colleagues reported online in the Journal of Clinical Psychiatry.

This remission was maintained in two patients for at least 3 months after ketamine was stopped. Both patients also achieved depression remission with a Hamilton Depression Rating Scale [HDRS28] score of <7, the study showed.
Ketamine “provides promise for the rapid treatment of suicidal ideation in medicated outpatients with treatment-resistant depression and suicidal thoughts,” the researchers wrote. “Larger controlled studies (including more serious/acute patients in the emergency room) are necessary to study ketamine’s anti-suicidal effects and the relationship between antisuicidal and antidepressant effects.”
C-SSRS Ideation score fell by an average of -0.27 per patient after each infusion (P<0.01), and HDRS28-Suicidal Ideation scores also fell significantly during the acute treatment phase (P<0.001), they reported.
Although this treatment for depression is not FDA-approved, this is an important study with relevant preliminary findings, Mark Frye MD, director of the Mayo Clinic Depression Center in Rochester, Minn., told MedPage Today.
“There is increasing interest in looking at clinical designs to sustain the robust antidepressant response (with associated reduction in suicidal thinking) that is increasingly recognized with intravenous ketamine,” Frye, who wasn’t involved in the study, said in an email. “Further research is encouraged to confirm these findings and if so, how best to then implement this potentially life-saving treatment for patients struggling with depression.”

“Suicidal ideation can be treated and this is just one strategy,” Maria Oquendo, MD, of New York Presbyterian/Columbia University Medical Center, told MedPage Today in an email. “While repeat doses of ketamine as a treatment strategy is not ready for prime time, the data suggest that we will be able to find suitable treatments for acute suicidal crises in the near future.”
Importantly, these data emphasize that looking at suicidal ideation as a symptom of depression “is too limited,” Oquendo added.
“These findings confirm multiple observations about the utility of ketamine in decreasing suicidal ideation independently of any effect on mood symptoms,” she said. “That is important for many reasons, not the least of which is that the pathophysiology of suicidal ideation and behavior is separate from that of mood disorders.”
Although preclinical study findings raise serious questions about the safety of chronic ketamine use, newer intranasal versions of ketamine are being investigated, Oquendo noted, adding that the field “anxiously awaits the results.”
In the meantime, psychosocial treatments also can be used to directly address suicidal ideation, she said.

“Referring patients to Dialectical Behavioral Therapy or implementing Safety Planning can help patients and their families manage chronic suicidal ideation,” said Oquendo, who was not involved in the study.
In the study, 14 outpatients with DSM-IV-diagnosed major depressive disorder were recruited between April 2012 and October 2013. All had current, stable suicidal thoughts of 3 months’ duration or longer. Over a period of 3 weeks, the patients received open-label ketamine infusions. The first 3 infusions consisted of 0.5 mg/kg over 45 minutes while the last 3 consisted of 0.75 mg/kg over 45 minutes.
Suicidal ideation was assessed 4 hours after ketamine infusion and after a follow-up of 3 months, using the C-SSRS and the HDRS28-SI.
Ionesco and colleagues pointed out that patients were recruited specifically for having thoughts of suicide, whereas in previous studies of ketamine, this was one of the criteria for exclusion. In addition, half of the patients were also taking benzodiazepines. Concomitant benzodiazepine use “may actually attenuate ketamine’s antidepressant effects, thereby making our preliminary significant findings of potential interest.”
Limitations of the trial included its small size, open-label design, lack of a placebo group, and the absence of mood ratings prior to infusions, the researchers said.