Psych News PsychoPharm Reports on Why FDA Took Steps To Encourage Removal of Opana ER From Market

When Endo Pharmaceuticals earlier this month announced that the company was pulling its opioid analgesic Opana ER (oxymorphone hydrochloride extended release) from the market, it marked the end of the road for a reformulated medication whose abuse by injection has been associated with multiple disease outbreaks.

“We are facing an opioid epidemic—a public health crisis, and we must take all necessary steps to reduce the scope of opioid misuse and abuse,” FDA Commissioner Scott Gottlieb, M.D., said in a press release announcing the agency’s formal request in June that Endo stop selling the medication. The action by the FDA was “the first time the agency has taken steps to remove a currently marketed opioid pain medication from sale due to the public health consequences of abuse,” the release stated.

While other opioids such as morphine and oxycodone are also abused, an article appearing today in Psychiatric News PsychoPharm describes how the Opana ER tablet is somewhat unusual: contributing to some of its deadly consequences are the inactive ingredients.

The older version of Opana ER tablet, which had been on the market from 2006 to 2011, was a simple formulation that released a small and steady amount of oxymorphone over 12 hours to maintain continuous pain relief. In 2012, after reports of people abusing the medication by crushing the tablet and snorting the powder, Endo replaced the original Opana ER tablet with a new formulation that contained a polymer known as polyethylene oxide (PEO) to make the tablet difficult to crush. If mixed with water, the tablet turns into a gel-like substance. The company had hoped to win the FDA’s “abuse-deterrent” label for this formulation, but the agency rejected the request, noting that it did not reach the standard for abuse deterrence.

Reformulated Opana ER deterred snorting, but individuals soon discovered that it was easier to “melt” and dissolve the tablet with heat. The liquid could be injected intravenously to produce the desired effect—a practice that led to more dangerous outcomes than snorting the tablets, Psychiatric News PsychoPharm reports. The article describes outbreaks of HIV and hepatitis C, as well as cases of a serious blood disorder known as thrombotic microangiopathy that can be traced back to injection abuse of Opana ER.

For more information on oxymorphone, the FDA’s action, and a list of 10 opioid analgesic products that have received the designation by the FDA as being “abuse deterrent,” see the full article here.

Today’s issue of Psychiatric News PsychoPharm also includes information on when to recommend SAMe for depression, findings that suggest imipramine may benefit patients with multiple somatic disorders, and more.

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‘Willingness’ May Predict How Well Patients With Severe OCD Respond to ERP Therapy

Willingness to experience unpleasant and unwanted thoughts, emotions, and bodily sensation during an exposure appears to improve exposure therapy outcomes among patients with severe obsessive-compulsive disorder (OCD), according to an article published July 17 in Depression and Anxiety.

“Data indicated that individuals with higher willingness during ERP [exposure and response prevention] reported faster symptom reduction during residential treatment, even when controlling for length of stay, psychopharmacological intervention, depression, adherence, and rituals performed during ERP,” Adam M. Reid, Ph.D., of the OCD Institute for Children and Adolescents at McLean Hospital and colleagues wrote.

Reid and colleagues set out to explore why ERP—considered the gold-standard psychotherapeutic treatment for OCD—is not fully effective for more patients with OCD. ERP is considered effective for about 50% to 80% of adults with OCD.

Previous research by others on acceptance and commitment therapy suggested that willingness is a marker of acceptance and is associated with improved engagement in distressing tasks. Reid and colleagues decided this would be an important factor on which to focus for their ERP research.

For the current study, 288 adults seeking treatment at an intensive/residential treatment (IRT) program for OCD participated in 4 hours of ERP per day for six weeks. About 25% to 50% of the sessions were led by trained clinical residence counselors or practicum students, and the remainder were self-directed. During each coached exposure session, coaches asked patients to rate how willing they felt before and during the exposure, as well as how willing they would be to repeat the exposure in the future. Willingness was rated on a scale of 0 (not at all willing) to 100 (extremely willing). The 10-item Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was used for assessing symptom severity.

Average Y-BOCS scores at baseline were 25.42, indicating that the average patient in the study had clinically severe OCD. After six weeks of ERP, OCD symptoms fell an average of 8.16 points on the Y-BOCS, resulting in an average reduction of 31% in symptoms. Higher willingness to engage in ERP was associated with more adherence, less ritualizing, and more habituation during ERP.

Reid and colleagues also asked patients to self-report their willingness to engage in ERP at three different time points: before ERP, immediately after, and for future exposures. Higher willingness at each time point was found to be associated with faster symptom reduction during six weeks of residential-level exposure therapy.

“Perhaps patients with higher willingness are more amenable to facing a higher number of novel stimuli and environments during exposure therapy,” the authors wrote. “[W]illingness may provide a clinical marker of exposure response that can be feasibly captured by clinicians in a naturalistic clinical setting.”

For related information, see the Psychiatric News article “Report Highlights Alternative Treatment Options for OCD.”

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Brain Imaging Offers Clues About PTSD Patients Most Likely to Benefit From Prolonged Exposure Therapy

Brain imaging may be able to predict patients with posttraumatic stress disorder (PTSD) who are most likely to benefit from the trauma-focused psychotherapy known as prolonged exposure, according to a study published yesterday in AJP in Advance.

Prolonged exposure—which helps patients confront trauma memories and real-life situations that provoke symptoms—is known to be an effective treatment for PTSD, but many patients fail to respond to this therapy. Senior author Amit Etkin, M.D., Ph.D., of Stanford University School of Medicine and colleagues used functional MRI (fMRI) to examine brain activity in 66 patients with PTSD before prolonged exposure to see if there were functional differences between the brains of patients who responded to prolonged exposure therapy and those who did not.

The patients underwent fMRI while resting and while carrying out tasks meant to elicit emotional response and regulation when presented with a series of happy, fearful, or neutral facial images and negative or neutral photographs. The patients were then randomly assigned to immediate prolonged exposure treatment (nine to 12 90-minute prolonged exposure sessions held once or twice a week) or a waiting-list condition. Four weeks after the final treatment session or comparable waiting period, all participants completed a posttreatment clinical assessment.

Patients who received prolonged exposure therapy demonstrated a greater reduction in PTSD symptom scores than those assigned to the waiting list. Those with greater baseline dorsal prefrontal activation and less left amygdala activation during emotion reactivity tests showed larger reductions in symptom scores after treatment, the authors reported. Similarly, individuals with greater baseline ventromedial prefrontal/ventral striatal activation during implicit regulation of emotional conflict demonstrated larger symptom reductions after treatment.

According to Etkin and colleagues, the findings suggest that “an individual’s capacity to benefit from exposure therapy is gated by [the] degree of spontaneous prefrontal control over amygdalar threat detection signals during incidental processing of a fear-conveying stimulus and the brain’s capacity to reduce interference from an emotional cue in the environment.” 

“This study provides a solid footing for understanding mechanisms so we can start working toward matching people to the treatment most likely to work for them and develop novel therapeutics for directly targeting brain therapy,” said Etkin. “By grounding psychotherapy in brain mechanisms, we can also hopefully decrease stigma, an invisible barrier to care that is so prevalent in psychiatric disorders and prevents people from getting the care that would benefit them.”

In an accompanying paper in AJP, Etkin and colleagues describe how imaging also revealed changes in the frontopolar cortex (the front-most portion of the prefrontal cortex) of PTSD patients who received prolonged exposure.

For related information, see the Psychiatric News article “Brain Scans May Indicate Optimal Treatment for Depression.”

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Digital Ads Offer Cost-Effective Strategy for Engaging Users About Early Psychosis

Using digital advertising is a successful and cost-effective strategy to engage individuals who are searching for mental health information online, reports a study published Monday in Psychiatric Services in Advance.

A team at the Zucker Hillside Hospital in Glen Oaks, N.Y., employed Google AdWords—clickable ads that appear when online searches match selected keywords—to raise awareness about early psychosis and encourage people to contact their local intervention clinic. 

“Although advertisers have long used the Internet to target consumers directly beyond the capabilities of traditional media, limited efforts have focused specifically on applying available technology to target and identify help-seeking individuals in real time and refer them to appropriate resources,” Michael Birnbaum, M.D., and colleagues wrote. 

Birnbaum and colleagues selected more than 2,000 keywords across 15 psychosis-related themes. General terms such as “psychosis,” as well as more specific terms such as “hearing voices” and “mind control,” were included to target both individuals searching for information for themselves and persons searching on behalf of a loved one. They next created 154 ads consisting of a headline related to the user’s search, description line, and call to action. The ads linked to a dedicated landing page that offered links to Northwell Health’s Early Treatment Program (ETP); an online form for submitting questions to ETP staff; and the Prodromal Questionnaire–Brief (PQ-B), an evidence-based screening tool that visitors to the page could use to assess psychosis risk. Google analytics were used to record Web site engagement. 

The digital campaign ran for 14 weeks and cost $1,427. During the campaign period, the early intervention ads appeared 191,313 times and received 4,350 clicks (2.3% click rate), resulting in an average cost of 33 cents per click. Once on the landing page, 44% (1,918) of users obtained psychosis-specific informational materials, 15% (671) completed an online psychosis self-screener, and 1% (57) contacted the ETP, which translates to $25 spent per desired outcome.

Compared with the industry average among health and medical campaigns, this project had favorable outcomes in terms of click rate (2.3% versus 1.8%), cost per click (33 cents versus $3.17) and cost per outcome ($25 versus $126.29), the authors reported.

“It is possible that the leap between searching for information online and making contact with a clinical team is too big for many individuals as an initial step,” Birnbaum and colleagues wrote. “Intermediate steps toward treatment in the form of digital engagement tools would also allow researchers to learn more about what users are seeking and why, as well as the barriers they face in considering treatment for psychosis.”

To read more about early psychosis intervention, see the Psychiatric News article “Early Identification of People With Psychosis Linked to Educating Outpatient Providers.”

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Members Urged to Contact Senators While McCain Recuperates

The Senate Republican health care reform bill, titled the Better Care Reconciliation Act (BCRA), appears to be on hold indefinitely until Sen. John McCain (R-Ariz.) returns to the Senate from surgery for a blood clot.

At press time, it was uncertain whether the bill would garner the necessary 50 votes for passage, even if McCain were available. In the meantime, however, APA continues to urge members to contact their Senators to voice opposition to the bill and use this delay to continue to voice their concerns. 

The BCRA, revised after an earlier version of the bill failed to make it to the Senate floor in June, retains some of the most problematic aspects of the original bill. These include deep cuts to Medicaid and the ability to waive the “essential health benefits” that must be covered in plans under the Affordable Care Act (ACA), including benefits for mental health and substance use disorders treatment.

Based on analysis by APA staff, the bill proposes to do the following:

• Fundamentally alters the payment structure of the Medicaid program. Beginning in FY 2020, state Medicaid programs will be funded on a fixed per-beneficiary basis (that is, a per capita cap). 
• Phases out Medicaid expansion made available to states under the ACA. States will no longer be able to expand eligibility for their Medicaid programs on January 1, 2020.
• Establishes an optional block grant program called the Medicaid Flexibility Program.
• Adds administrative costs and burdens to Medicaid programs. The BCRA requires states to reassess enrollees’ Medicaid eligibility once every six months. It would also give states the option of requiring nondisabled, nonelderly, and nonpregnant individuals to satisfy work requirements as a condition for eligibility.

Also under consideration is a controversial amendment to the bill proposed by Sen. Ted Cruz (R-Tex). The amendment would allow insurers to offer plans that do not comply with the ACA’s mandatory coverage provisions, including the requirement that plans cover certain “essential health benefits,” the prohibition against insurers increasing premiums for individuals with pre-existing conditions, and the requirement that plans offer a free annual preventative care visit to enrollees.

APA Department of Government Relations staff have prepared a detailed analysis of the bill as well as a side-by-comparison of all of the health reform proposals in play: the existing Affordable Care Act, the House-passed American Health Care Act, the initial version of BCRA from June, and the revised BCRA now pending in the Senate.

To make contacting your senator as easy as possible and voice your opinion, APA has established a special portal on the APA website that provides messaging and contact information specifically for your senators.

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APA Calls on Senate to Reject Latest Republican Health Care Reform Bill

APA is urging members to contact their U.S. senators and voice their opposition to the new Senate health care reform bill, released yesterday by Senate Majority Leader Mitch McConnell (R-Ky).

Senate Republicans released a revision of the Better Care Reconciliation Act (BCRA), the original version of which never made it to the Senate floor for a vote when it became clear that the bill would fall short of 50 votes. The revised BCRA was introduced after McConnell announced he was delaying the start of the August recess by two weeks (until August 14) to allow more time to address the legislation.

The new BCRA still includes provisions that are deeply problematic, especially for individuals with serious mental illness and substance use disorders. The bill retains the deep Medicaid cuts that were a feature of the original reform bill and permits the removal of the essential health benefits. Both are significant concerns to APA.

“Wordsmithing and throwing money at certain constituencies to gain more votes highlights a deeply flawed Senate proposal that is insufficient,” said APA CEO and Medical Director Saul Levin, M.D., M.P.A., in a statement released yesterday. “The changed bill still rolls back access to care and allows for the removal of essential health benefits, such as treatment for mental illness and substance use disorders, that will affect millions of patients and their families—from the young to the elderly to the most vulnerable in all our communities.”

APA staff are continuing to analyze the bill. An updated cost estimate by the Congressional Budget Office is expected early next week, with Senate leadership planning a procedural vote on Tuesday or Wednesday to determine whether to proceed to debate on the bill.

APA will continue to actively engage the Senate and participate as part of a “Frontline Physician” coalition with five other groups (the American Academy of Family Physicians, American Academy of Pediatrics, American College of Physicians, American College of Obstetricians & Gynecologists, and American Osteopathic Association) to express concerns with the legislation and urge senators to vote no on the bill. Yesterday, Immediate Past APA President Maria A. Oquendo, M.D., Ph.D., joined leaders of these organizations on Capitol Hill to visit key Senate offices.

APA members are urged to contact their senators through a special portal on the APA website.

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Antidepressant Use in Pregnancy and Intellectual Disability in Offspring Not Associated, Concludes Study

An international team of researchers analyzing data from a large Swedish national registry concluded there is no association between antidepressant use during pregnancy and intellectual disability in offspring. The report was published yesterday in JAMA Psychiatry.

Researchers led by Alexander Viktorin, Ph.D., of the Department of Psychiatry at the Icahn School of Medicine at Mount Sinai, analyzed data from the Swedish Prescribed Drug Register and the Swedish National Patient Registry to estimate relative risks (RRs) for intellectual disability in children exposed during pregnancy to antidepressant medication. They also analyzed the risk associated specifically with selective serotonin reuptake inhibitor (SSRI) antidepressants, all other non-SSRI antidepressants, and other nonantidepressant psychotropic medications.

Intellectual disability was defined as having at least one inpatient or outpatient specialist care admission between birth and the end of follow-up at December 31, 2014, with an ICD-10 code of F70 to F79.

Of the 179,007 children in the study, an intellectual disability was diagnosed in 0.9% of those exposed to antidepressants and in 0.5% of those not exposed. The unadjusted RR of intellectual disability in the children exposed to maternal antidepressant medication use during pregnancy was estimated at 1.97. However, when the data were adjusted for parental age, the psychiatric illness for which the mother was treated, and other variables unrelated to the medication, the increased risk disappeared and the relative risk was statistically nonsignificant.

Moreover, the analyses of risks for children born to mothers treated during pregnancy specifically with SSRI antidepressants, non-SSRI antidepressants, or nonantidepressant psychotropic medications were comparable to the analyses of children exposed to any antidepressant during pregnancy.

For related information see the Psychiatric News article “SSRI Use During Pregnancy May Increase Risk of Language Delays in Offspring.”

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