Tamoxifen May Reduce Mania in Patients With Bipolar Disorder But Questions Remain

Tamoxifen, a medication commonly used to treat breast cancer, appears to hold some promise as a treatment for mania, according to a systematic review and meta-analysis appearing in the Journal of Psychopharmacology.

Tamoxifen has been proposed as a treatment for bipolar disorder because it acts on cells in a way similar to lithium and valproate—both of which are effective medications for bipolar disorder. However, the current review found most studies focused on the effect of tamoxifen on mania, not on bipolar disorder, and its effects on depression are unknown.

“Tamoxifen appears to be a promising potential treatment for episodes of mania,” wrote Jorge Palacios, M.D., of King’s College, London, and colleagues. “However, the total number of participants in trials to date remains relatively low … and there has been a lack of study of its effects on depressive mood.”

Palacios and colleagues performed a literature search using the Cochrane Central Register of Controlled Trials and other resources for randomized, controlled trials (RCTs) of tamoxifen for bipolar disorder. They identified five placebo-controlled RCTs of tamoxifen in the treatment of acute mania in adults. There were no randomized trials of the agent for bipolar depression or for relapse prevention.

The five placebo-controlled RCTs included in the meta-analysis ran for a duration of three to six weeks and included a total of 164 participants. Tamoxifen was studied as a monotherapy in two of the studies and as an adjunct to lithium or valproate in the other three.

Tamoxifen was found to be superior to placebo in lowering mania scale scores, with greater improvements when used as a monotherapy. Response rates (defined as at least a 50% reduction in the mania rating scale score from baseline to end of treatment) were also higher for patients randomized to tamoxifen, and the overall acceptability (measured by overall drop-out rates) was similar to placebo.

“Tamoxifen has been recommended as an option for pharmacological treatment of acute mania in some, but not all recent guidelines,” the authors wrote. “There remain important unanswered questions to clarify its appropriate use. Future studies could investigate the effects of tamoxifen as an adjunct to dopamine antagonist medications for improved antimanic efficacy and establish its longer-term effects on mood, particularly depression, and relapse.”

For more information, see the Psychiatric News article “Researchers Sum Up Current Knowledge of Bipolar Disorder, Call for More Study.”

(Image: istock.com)

Follow Psychiatric News on Twitter!

Teen Marijuana Users Face Higher Risk of Adult Depression, Suicidality, Meta-Analysis Suggests

Teenagers who use cannabis are at a significantly higher risk of developing major depression and suicidality as young adults, including a three-times greater risk of attempting suicide, according to a meta-analysis published yesterday in JAMA Psychiatry.

“Cannabis is the mostly commonly used drug of abuse by adolescents in the world,” wrote Gabriella Gobbi, M.D., Ph.D., of McGill University in Montreal, Canada, and colleagues. The authors systematically selected studies that assessed participants’ cannabis use when they were younger than 18 years old; adjusted for depression, anxiety, and/or suicidality at baseline; and tracked development of depression in young adulthood (age 18 to 32 years). The meta-analysis included seven studies for depression, three for anxiety, three for suicidal ideation, and three for suicide attempts, totaling some 23,000 participants.

The odds of developing depression in young adulthood was more than one-third higher among adolescents who used cannabis before age 18 (odds ratio [OR] = 1.4), compared with those who had not. The effect was more dramatic for suicidality: adolescents who used cannabis before age 18 were 50% more likely to think about suicide (pooled OR of 1.5) and more than three times more likely to have attempted suicide (pooled OR of 3.5) as young adults.

Younger users of cannabis, age 14 and 15, were at significantly higher risk of suicidal behaviors, according to the report, and girls seemed more susceptible than boys to develop adult depression if they smoked cannabis in adolescence, the researchers reported. “Two trajectory studies demonstrated that quitting cannabis by the end of adolescence did not protect people from some of the serious effects of the drug,” the authors added.

More than one-third of high school seniors reported using marijuana in 2018 (36%), with vaping of THC (the active ingredient in marijuana) rising at record levels, according to an annual National Institute on Drug Abuse-funded survey. At the same time, perceptions of harm and disapproval of marijuana use have trended down in recent years, with only 1 in 4 seniors agreeing that regular marijuana use poses a great risk—less than half of what it was 20 years ago. Ten states plus the District of Columbia have now legalized recreational use of marijuana for adults in 2019.

“These findings highlight the importance of initiatives aiming to educate teenagers on the risks associated with using cannabis and teach them skills to resist peer pressure,” Gobbi and colleagues concluded from their study. “Given the likelihood of a window of risk during adolescence when the deleterious effects of cannabis are most pronounced, the findings in this meta-analysis suggest that cannabis is a serious public health concern and there is an urgent need to implement better drug use prevention programs targeting the use of cannabis among adolescents and interventions aimed at educating adolescents to develop the skills to resist peer pressure on drug consumption.”

For more information, see the Psychiatric News article “Teen Vaping Surges While Use of Most Other Substances Flat” and the American Journal of Psychiatry article “A Population-Based Analysis of the Relationship Between Substance Use and Adolescent Cognitive Development.”

(Image: iStock/Stígur Már Karlsson/Heimsmyndir)

Follow Psychiatric News on Twitter!

FDA Advisory Panel Gives Nod to Esketamine Nasal Spray, Paving Way for FDA Approval

An independent advisory panel to the Food and Drug Administration (FDA) on Tuesday endorsed the esketamine nasal spray Spravato for the treatment of adults with treatment-resistant depression. The rapid-acting antidepressant was developed by the Janssen Pharmaceutical Companies of Johnson & Johnson. While the FDA is not required to follow the recommendation of the panel, the agency does take its advice into consideration.

In a 14-2 vote with one abstention, the Psychopharmacologic Drug Advisory Committee and Drug Safety and Risk Management Advisory Committee concluded the benefits of esketamine outweigh the risks.

The committees’ vote on the safety and effectiveness of esketamine was based in part on the results of five phase 3 studies of esketamine in patients with treatment-resistant depression. As described in background materials made available on the FDA website ahead of the meeting, these studies included three short-term, double-blind, placebo-controlled studies; one randomized withdrawal maintenance-of-effect study; and one long-term, open-label safety study. To participate in these studies, patients were required to have failed at least two prior antidepressant trials at study entry. In each trial, patients were assigned to receive esketamine or placebo in addition to a newly initiated oral antidepressant.

According to the FDA briefing document, the evidence in support of esketamine’s effectiveness derives primarily from two positive phase 3 trials, which showed that treatment with esketamine nasal spray plus a newly initiated oral antidepressant was associated with rapid reduction of depressive symptoms and delayed time to relapse of symptoms of depression compared with placebo nasal spray plus a newly initiated antidepressant.

The safety profile of esketamine was evaluated in both short- and long-term trials, which concluded that the medication was generally tolerable in patients with treatment-resistant depression. The most common adverse events reported by patients in the trials included sedation, dissociation, and increases in blood pressure, with the symptoms most commonly presenting in the two hours following drug administration.

Because esketamine is a similar compound to ketamine—a drug known to be popular for recreational use for its ability to produce “out-of-body” experiences and hallucinations—some experts have expressed concerns about the risks of misuse and abuse. In briefing materials submitted by Janssen ahead of yesterday’s meeting, the company stated, “While the potential for abuse, misuse, and diversion exists for esketamine due to its similar pharmacologic profile to ketamine, no evidence of abuse, misuse, or overdose was observed in the esketamine development program with a [treatment-resistant depression] population (note, patients with moderate to severe substance use disorder were excluded from the studies), and possible diversion was minimal (<0.1% clinical supply kits unaccounted for in the Phase 3 studies).”

The FDA is proposing a Risk Evaluation and Mitigation Strategy (REMS) to ensure safe use of esketamine. “Among the key elements of the proposed REMS, esketamine administration would occur only in certain health care settings where the patient could be monitored for two hours after administration, the drug would not be dispensed directly to patients, and patients would be enrolled in a registry to better characterize the risks associated with esketamine administration,” the FDA briefing document noted.

Esketamine, an antagonist of the N-methyl-D-aspartate (NMDA) receptor, was first granted an FDA breakthrough therapy designation for treatment-resistant depression in 2013 and for major depressive disorder with risk of suicide in 2016. According to Janssen, the decision by the FDA on whether to approve the medication is expected by March 4.

For related information, see the American Journal of Psychiatry article “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.”

(Image: iStock/zoljo)

Follow Psychiatric News on Twitter!

APA Announces Results of 2019 Election

APA’s Committee of Tellers has approved the following results of APA’s 2019 national election. Please note that these results are considered public but not official until approved by the Board of Trustees at its meeting on March 9 and 10 in Washington, D.C.



President-Elect
Jeffrey Geller, M.D., M.P.H.

Secretary
Sandra DeJong, M.D., M.Sc.

Minority/Underrepresented Trustee
Rahn Kennedy Bailey, M.D.

Area 3 Trustee
Kenneth Certa, M.D.

Area 6 Trustee
Melinda Young, M.D.

Resident-Fellow Member Trustee-Elect
Michael Mensah, M.D., M.P.H.

Complete results of the election will be reported in the March 1 issue of Psychiatric News.

---

Annual Meeting Early Bird Registration Ends Today

Time is running out to take advantage of the lowest registration rates for the 2019 Annual Meeting in San Francisco. Register before the end of the day today, February 12, to save.

Follow Psychiatric News on Twitter!

Text Messaging May Enhance Postpartum Depression Screening

Using text messages to ask questions and educate women with a new baby about postpartum depression is a practical and feasible approach to improve postpartum depression screening, reports a study in Psychiatric Services in Advance.

“This cost-effective, innovative technology has excellent potential to be used in mental health care for universal screening purposes and as a first step in the pathway to treatment,” wrote Andrea Lawson, Ph.D., of Mount Sinai Hospital in Toronto and colleagues.

The researchers recruited 937 new mothers to participate in a 12-week long assessment of a text-based screening. Every two weeks, the women were asked by text to rate how often they had experienced little interest or pleasure in doing things over the past two weeks and how often they had felt depressed or hopeless. The participants also received three text messages per week aimed at increasing awareness about postpartum depression and encouraging self-care.

Women who screened positive for depression based on their responses to the biweekly text-based screening were contacted by a researcher who administered the Edinburgh Postnatal Depression Scale—a 10-item screen considered the gold-standard postpartum diagnosis tool—via telephone. A subset of women who screened negative on the text-based screening were also screened using the Edinburgh Postnatal Depression Scale to help determine the accuracy of the text-based approach.

By comparing the results of the screening texts with the Edinburgh Postnatal Depression Scale diagnoses, the researchers found that the text-based screening was moderately accurate; 18% of the women who screened positive for depression based on their text answers and 10% who screened negative were misclassified.

While Lawson and colleagues acknowledged that the 18% false-positive rate of the text-based screening “was not ideal,” they noted that avoiding false-negatives is more important for this initial screening whose aim is not diagnosis but rather identification of women who need further follow-up.

The text-based screening was well-received; of the 937 participants who completed the study, 930 (99%) responded to a minimum of one of the six texted screens, and 632 (67%) responded to all six. A post-study survey also showed that 78% of the participants would recommend using text messages to screen for postpartum depression.

“We believe the reasons for the high rate of responsivity to the screen were its brevity and the fact that in-person attendance was not a requirement for completion,” the authors wrote. “The postpartum stage is a very difficult time for a mother, frequently characterized by sleep deprivation and high stress levels. Completing lengthy assessment tools in-person at this time can be challenging, particularly among mothers who are experiencing symptoms of depression.”

To read more about postpartum depression screening, see the Psychiatric News article “Researchers Turn to Smartphone Apps to Learn About Postpartum Depression.”

(Image: iStock/Halfpoint)

---

Annual Meeting Early Bird Registration Ends Tuesday, February 12

Time is running out to take advantage of the lowest registration rates for the 2019 Annual Meeting in San Francisco. Register before the end of the day on Tuesday, February 12, to save.

Follow Psychiatric News on Twitter!

Chronic Sinusitis Linked to Depression, Anxiety, Study Finds

People who have chronic rhinosinusitis (commonly referred to as chronic sinusitis and characterized by inflammation of nasal passages lasting more than 12 weeks) may be more likely to have depression and anxiety, according to a study published yesterday in JAMA Otolaryngology–Head & Neck Surgery.

Jong-Yeup Kim, M.D., Ph.D., of Hallym University College of Medicine, in South Korea and colleagues analyzed the health insurance records of 16,244 South Korean patients who received inpatient and outpatient care for chronic rhinosinusitis from January 2002 through December 2004. Each patient was tracked until December 31, 2013, or until the occurrence of depression and anxiety. The researchers then compared the rates of depression and anxiety in this group with those of 32,448 patients who did not have chronic rhinosinusitis in that period.

During the follow-up period, there were 24.2 incidences of depression per 1,000 person-years in the chronic rhinosinusitis group, compared with 16 in the control group. There were 42.2 incidences of anxiety per 1,000 person-years in the chronic rhinosinusitis group, compared with 27.8 in the control group.

In their discussion, the researchers noted that although people with chronic rhinosinusitis have higher rates of depression and anxiety, the relationship between chronic rhinosinusitis and these conditions remains unclear: “Despite its clinical importance, the causal association between [chronic rhinosinusitis] and psychiatric comorbidities is not fully understood. For example, whether depression and anxiety amplify the symptoms of [chronic rhinosinusitis] or whether these conditions are the consequence of [chronic rhinosinusitis] is unknown,” they wrote.

In an accompanying editorial, Edward D. McCoul, M.D., M.P.H., of the Ochsner Clinic in New Orleans noted that it may be helpful for physicians to keep depression and anxiety in mind when treating patients with chronic rhinosinusitis.

“Given the current state of knowledge, the physician may choose to screen patients with newly diagnosed [chronic rhinosinusitis] for the presence of depression or anxiety disorders. Brief, patient-reported questionnaires are a low-cost measure that may reduce morbidity in the long term and improve the success of treatments directed at [chronic rhinosinusitis],” he wrote.

(Image: iStock/Cecilie_Arcurs)

Follow Psychiatric News on Twitter!

Intervention for Suicidal Adolescents May Reduce Long-Term Mortality

Suicidal adolescents who took part in a program for which they chose several “caring adults” who stayed in regular contact with them and were supportive of their treatment were nearly seven times less likely to die during the follow-up of 11 years to 14 years, according to a study published Wednesday in JAMA Psychiatry.

The intervention is believed to be among the first aimed at suicidal adolescents that has shown a reduction in mortality, according to lead author Cheryl A. King, Ph.D., of the University of Michigan and colleagues.

The study was a secondary analysis of a trial involving more than 400 adolescents, aged 13 to 17, who were hospitalized on a psychiatric unit for serious, frequent thoughts about killing themselves or a suicide attempt. The original study comparing adolescents who received Youth-Nominated Support Team–Version II (YST)—a psychoeducational, social support intervention—with those in a control group found that YST was associated with a significant reduction in suicidal ideation.

With YST, the adolescents nominated three or four “caring adults,” such as parents, grandparents, coaches, teachers, parents of friends, and youth group leaders who attended a one-hour psychoeducational session. During the session, the adults learned about the youth’s treatment plan, suicide warning signs, how best to communicate with the adolescents, and ways to increase the likelihood of youth’s adherence to their treatment plan. The adults received weekly supportive calls from YST staff for three months and engaged in regular contact with the youth.

For the current study, King and colleagues examined the National Death Index and found there were 13 deaths among participants in the control group, compared with two deaths in the YST group, meaning that those in the control group had a nearly sevenfold higher risk of dying within the 11 years to 14 years of follow-up. The authors noted that although the confidence interval was wide (1.5-29.3), reflecting the relatively small number of deaths, even the lower end of the confidence interval indicated a 50% higher mortality in the control group. All deaths occurred when participants were between the ages of 18 years and 28 years.

When the authors looked only at suicide, there was not a significant difference between the groups (three suicides in the control group versus one suicide in the YST group). Most of the deaths in the control group (nine) were drug related or caused by drug overdose.

“Although YST was not associated with fewer deaths coded as suicides…, this secondary analysis of mortality outcomes indicates that YST may be associated with positive youth trajectories and reduced mortality. Future studies are needed to replicate our study findings and examine YST’s mechanisms of action, which are suggested by its psychoeducational component, its underlying social support conceptual model, and the study results indicating that YST was associated with more outpatient psychotherapy, medication follow-up, and drug treatment,” King and colleagues wrote.

For related information, please see the American Journal of Psychiatry article “Suicide Attempt Prevention: A Technology-Enhanced Intervention for Treating Suicidal Adolescents After Hospitalization.”

(Image: iStock/kali9)

Follow Psychiatric News on Twitter!