Monday, March 27, 2017

Duloxetine, Venlafaxine May Be Most Effective at Reducing Diabetic Nerve Pain

The serotonin-norepinephrine reuptake inhibitors duloxetine and venlafaxine appear to have the best evidence for being effective at reducing nerve pain in people with diabetes, according to a meta-analysis published in Neurology. Duloxetine is FDA-approved for treating pain in diabetic neuropathy, though venlafaxine is not.

The researchers pooled together data from 106 clinical studies published between 2011 and 2015 examining the effectiveness of pharmacologic approaches to improving pain in patients with diabetic peripheral neuropathy. The analysis compared outcomes in patients taking 21 different medications, though the authors were unable to draw conclusions for any head-to-head drug comparisons due to insufficient evidence.

The researchers found moderate evidence to suggest that duloxetine and venlafaxine were more effective at reducing neuropathy-related pain than placebo. Tricyclic antidepressants, botulinum toxin, the opioids tramadol and tapentadol, and the anticonvulsants pregabalin and oxcarbazepine were also found to be more effective than placebo, but the evidence base for these medications was weak.

In contrast, the anticonvulsant gabapentin, mood stabilizer valproate, and capsaicin cream were all found to be no more effective than placebo; these findings run contrary to guidelines for treating diabetic peripheral neuropathy published by the American Academy of Neurology in 2011, which listed all three agents as probably effective.

“Our findings generally support the effectiveness of the three drugs approved by the Food and Drug Administration (FDA) for the treatment of pain in diabetic peripheral neuropathy: duloxetine, pregabalin, and tapentadol,” wrote Julie Waldfogel, Pharm.D., of the Johns Hopkins Hospital and her colleagues. “Additional studies evaluating longer term outcomes are needed to better inform clinical decision-making, patient choice, and clinical practice guidelines.”

To read more about treatment of patients with diabetes, see the Psychiatric News article “New Initiative Targets Psychosocial Issues Related to Diabetes.”

(Image: iStock/IPGGutenbergUKLtd)

Friday, March 24, 2017

Brain Scan May Help Predict Treatment Outcomes, Study Suggests

One of the challenging tasks in the psychiatric care of major depressive disorder is finding a treatment that will work for each patient without stepping through a series of failed alternatives first. A study published today in AJP in Advance suggests patterns of activity on brain scans may offer clues about a patient’s probability of either remission or treatment failure.

Boadie Dunlop, M.D., M.S., and Helen Mayberg, M.D., both of Emory University School of Medicine, and colleagues assessed resting-state functional connectivity between the subcallosal cingulate cortex (SCC) and three other brain regions—the dorsal midbrain, the ventrolateral prefrontal cortex and anterior insula, and the ventromedial prefrontal cortex—in 122 patients with depression. The patients were then randomized to 12 weeks of cognitive-behavioral therapy (CBT) or to treatment with an SSRI or SNRI. There was no placebo arm in the trial.

“[N]egative connectivity scores were associated with remission to medication and treatment failure with CBT, whereas positive connectivity scores were associated with remission to CBT and treatment failure with medication,” wrote Dunlop and colleagues. “Brain-based measures of major depression are proving superior to clinical measures and patient preferences in signifying differential outcomes to depression treatments.”

The researchers noted that replication of this study using existing data or prospective trials is needed before this approach can be used in everyday practice.

“All depressions are not equal, and like different types of cancer, different types of depression will require specific treatments," said Mayberg said in a press release. "Using these scans, we may be able to match a patient to the treatment that is most likely to help [the individual], while avoiding treatments unlikely to provide benefit.”

For more in Psychiatric News about imaging and depression, see “Neuroimaging Reveals Depression Subtypes That Respond to TMS.”

(Image: Mary Rice/Shutterstock)

Thursday, March 23, 2017

APA Members Urged to Contact House Representative Now to Oppose AHCA

APA members are urged to call their congressional representative today to express opposition to the American Health Care Act (AHCA). The bill would partially repeal and replace the Affordable Care Act.

In a letter yesterday to Congressional leaders, APA President Maria A. Oquendo, M.D., Ph.D., and APA CEO and Medical Director Saul Levin, M.D., M.P.A., outlined APA's objections to the bill, which the Congressional Budget Office has estimated would eliminate coverage for some 24 million Americans.

Among APA's chief concerns are the proposed changes to Medicaid and private insurance that would disproportionately affect those with serious mental illness. “APA is not supportive of the changes to Medicaid and Medicaid financing contained within AHCA,” Oquendo and Levin wrote. “Unraveling the expansion of Medicaid coverage [under the ACA] threatens the 1.3 million Americans with serious mental illness and the 2.8 million Americans with substance use disorders who gained coverage for the first time under the expansion. Furthermore, the Medicaid financing provisions contained within the AHCA will eliminate the current requirement that states cover mental health services and reduce overall Medicaid funding by $880 million, or 25 percent, over 10 years.”

Additionally, Oquendo and Levin said APA is also not supportive of certain reforms to private insurance coverage that potentially stand to affect individuals with mental illness and substance use disorders disproportionately. “These include refundable tax credits that are on average significantly less generous than the current subsidies available for premium support and hefty premium surcharges for failing to maintain continuous coverage,” they wrote.

APA is also concerned about proposals to eliminate "essential health benefits" that were mandated for coverage under the ACA. Among these 10 essential benefits is coverage of treatment of mental illness and substance use disorders and include such services as depression screening for adults and adolescents, behavioral assessments for children, alcohol use screening and counseling for adults, alcohol and drug use assessments for adolescents, tobacco use screening for adults, and cessation interventions for tobacco users. 

In a press statement, Oquendo said, “We are willing to work with members of both parties in Congress so that more Americans have access to high-quality care. Unfortunately, we cannot support the AHCA bill because it is not a solution.”

APA members can access the phone number of their House representative at APA's Action Center

(Mikhail Kolesnikov/Shutterstock)

Wednesday, March 22, 2017

Suicide Risk After Violent Attempt Found to Be Highest Within First 30 Days

An article published yesterday in AJP in Advance suggests that people who survive violent self-harm events, particularly those involving self-inflicted firearm injuries, are at the greatest risk of suicide in the 30 days following an initial self-harm event. 

“Adults who present for treatment after a deliberate self-harm event offer opportunities for suicide prevention,” Mark Olfson, M.D., M.P.H., and colleagues wrote. “[C]linical priority should be given to developing and implementing prompt interventions that help ensure the safety of these high-risk patients during this high-risk period.”

For the study, Olfson and colleagues extracted Medicaid data on adults aged 18 to 64 with clinical diagnoses of deliberate self-harm (n=61,297). The self-harm cohort was followed forward from the index date for 365 days, date of death from any cause, or end of available data, whichever came first. A total of 243 deaths by suicide took place during the follow-up period.

The researchers reported that during the first year following the index self-harm event, the suicide rate for the follow-up cohort was 439.1 per 100,000 person-years—37 times greater than the suicide rate of the U.S. general population (11.8 per 100,000 person-years). Additional analysis revealed that self-harm patients who survived previous violent self-harm events as well as those who were male and older were at an elevated risk of suicide. Self-harm patients who used violent methods were at significantly increased risk of suicide during the first 30 days after the initial event compared with those who used nonviolent methods (hazard ratio=17.5, 95%; CI=11.2–27.3), but not during the following 335 days.

“This risk pattern supports concerted efforts to protect patients who attempt suicide by highly lethal methods during the acute period after the self-harm event. During periods of extremely high risk, inpatient admission may facilitate crisis work, intensive supervision, and implementation of complex interventions, and it can help ensure patient safety,” the authors wrote. “For patients who own firearms or live in homes with firearms, distributing trigger locks and urging family members to temporarily store household firearms away from the patient’s home can be a lifesaving intervention.”

For related information, see the Psychiatric News article “Firearms and Suicide: Risk Assessment and Management” and The Return on Investment of Postdischarge Follow-Up Calls for Suicidal Ideation or Deliberate Self-Harm.

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Tuesday, March 21, 2017

Valbenazine Found to Reduce Symptoms of Tardive Dyskinesia in Patients With Schizophrenia

Once-daily treatment with valbenazine (NBI-98854), a highly selective vesicular monoamine transport 2 (VMAT2) inhibitor, significantly reduced the symptoms of tardive dyskinesia (TD) compared with placebo in patients with schizophrenia, schizoaffective disorder, or a mood disorder, according to a study published today in AJP in Advance. The findings suggest the VMAT2 inhibitor, developed by Neurocrine Biosciences Inc., may be an effective treatment option for patients experiencing the involuntary, repetitive body movements associated with the disorder.

Research shows that approximately 1 in 4 patients with chronic exposure to antipsychotics develops TD. While there are several strategies for managing TD, to date no medications have been approved by the Food and Drug Administration (FDA) for the treatment of TD.

For the study, Robert Hauser, M.D., M.B.A., of the University of South Florida and colleagues randomly assigned 234 patients with schizophrenia, schizoaffective disorder, or a mood disorder to take valbenazine (40 mg/day or 80 mg/day) or placebo daily for six weeks. All patients in the trial had moderate-to-severe TD at screening, and approximately 85% were also taking antipsychotics throughout the trial. The researchers compared change from baseline in dyskinesia scores on the Abnormal Involuntary Movement Scale (AIMS, items 1–7) at two, four, and six weeks.

A total of 205 patients completed the study. The mean change from baseline to week six of the AIMS dyskinesia score was −3.2 for the 80 mg/day group, compared with −0.1 for the placebo group, a significant difference. The mean AIMS dyskinesia score was also reduced in the 40 mg/day group (−1.9 compared with −0.1). Valbenazine was generally well tolerated, with somnolence, akathisia, and dry mouth reported by 5.3%, 3.3%, and 3.3% of patients in both dosage groups, respectively.

“These findings add to a growing body of evidence showing that valbenazine is effective … at reducing the severity of movements in patients with moderate-to-severe TD,” said Stanley Caroff, M.D., an emeritus professor of psychiatry at the Perelman School of Medicine at the University of Pennsylvania, who not involved with the study. “Although many fundamental questions remain—including concurrent changes in antipsychotic and anticholinergic therapy, the course and outcome of TD in long-term investigations, and relative costs of treating TD—the availability of an agent that significantly suppresses manifestations of TD would be extremely valuable in reducing the stigma and embarrassment that accompanies TD, thereby enhancing social rehabilitation and recovery efforts," Caroff concluded.

In 2016, Neurocrine announced that the FDA was reviewing the company’s New Drug Application (NDA) for valbenazine for the treatment of TD. According to a press release by the company, the FDA is expected to reach a decision by April 11, 2017.

For related information, see the Psychiatric News article “New Hope for Patients With Tardive Dyskinesia,” by Stanley Caroff, M.D.

(Image: iStock/Portra)

Monday, March 20, 2017

5α-Reductase Inhibitors May Increase Risk of Self-Harm, Depression in Older Men

Although the 5α-reductase inhibitors (5ARIs) finasteride or dutasteride are known to lead to improvements in men with benign prostatic hyperplasia (BPH), postmarketing data have suggested that men taking the medications might be at a greater risk of suicide and self-harm. A study published today in JAMA Internal Medicine has found that men 66 and older who took 5ARIs were not at a significantly increased risk of suicide. However, the risk of self-harm and depression in men taking these medications increased during the first 18 months of use compared with men not exposed to the medications. 

“The recognition of depression and self-harm as potential adverse effects of 5ARIs is important given their significant impact. However, the relatively small magnitude of these risks should not dissuade physicians from prescribing these medications in appropriate patients,” Blayne Welk, M.D., an assistant professor of surgery at Western University in London, Ontario, and colleagues wrote. “This research may help physicians counsel patients on the risks of 5ARIs.”

Belk and colleagues compared administrative data available for 93,197 men aged 66 and older in Ontario who started taking a 5ARI between 2003 and 2013 with an equal number of older men not prescribed these medications. During the study period, there were a total of 38 suicides, 169 incidents of self-harm, and 1,750 cases of depression among the participants taking a 5ARI. 

There was no difference in suicide risk between the groups, but among men exposed to 5ARIs, there was a significantly increased risk of self-harm (hazard ratio [HR]=1.88; 95% confidence interval [CI]=1.34-2.64) during the first 18 months of use; this risk of self-harm did not remain significantly elevated after the initial 18 months. There was also a significantly increased risk of depression (HR=1.94; 95% CI=1.73-2.16) during the first 18 months of use, and this risk continued to be elevated after 18 months, though to a lesser degree (HR=1.22; 95% CI=1.08-1.37). Men taking finasteride or dutasteride appeared to be at similar risk of suicide, self-harm, and depression.

Because the absolute risk of self-harm and depression was found to be low, the researchers noted “the potential benefits of 5ARIs in this population likely outweigh these risks for most patients. … Discontinuation of the 5ARI may be appropriate in the setting of new-onset depression or self-harm after the initiation of a 5ARI.”

The authors noted that additional studies are needed to determine the risk of suicide, self-harm, and depression in younger men prescribed finasteride for hair loss.

For related information, see the Psychiatric News article “Large Trial Suggests Testosterone Offers Moderate Benefits.”

(Image: Diego Cervo/Shutterstock)

Friday, March 17, 2017

Rural Suicide Rates Outpaced Urban Rates From 1999 to 2015

Suicide rates in the United States increased steadily between 1999 and 2015, but the rates for less urban counties climbed faster than those for cities, according to a report today from the Centers for Disease Control and Prevention (CDC).

“[T]he gap in rates between less urban and more urban areas widened over time, and rates in medium metro, small metro, and non-metro areas increased at a more rapid pace beginning in 2007–2008,” wrote Scott Kegler, Ph.D., of the CDC’s Division of Analysis, Research, and Practice Integration, and two colleagues in Morbidity and Mortality Weekly Report.

Overall rates rose from an average of 12.6 per 100,000 in 1999-2007 to an average of 14.4 per 100,000 in 2008-2015. However, rates jumped from about 15/100,000 in rural areas in 1999 to about 22/100,000 in 2015. In large central metropolitan areas, the rate went from about 11/100,000 to 12/100,000.

Kegler and colleagues suggested that some of the factors associated with the disparity were shortages of clinicians in less urban areas, as well as limited access to mental health care, social isolation, and the effects of the opioid overdose epidemic and the 2007-2009 economic recession (which struck rural areas especially hard).

“There is a growing need for comprehensive suicide prevention employing a broad public health approach,” they concluded. Besides general anti-suicide strategies, additional help for rural areas might include increasing the number of health care providers through incentives, expanding the use of telepsychiatry, and promoting social connectedness.

For more in Psychiatric News about rural suicide prevention, see “Understanding Access to Means of Suicide Opens Door to Prevention.” See also "Preventing Suicide: A Technical Package of Policies, Programs, and Practices" from the CDC.

(Image: Atlantagreg/iStock)


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