Monday, February 23, 2015

Depression treatment: the evidence base from a primary care perspective

- Jennifer Middleton, MD, MPH

Most patients with depression receive treatment solely from a primary care physician. Family physicians have had to largely rely on studies and guidelines from psychiatric settings to make decisions about depression treatment, but a new systematic review, published in this month's Annals of Family Medicine, looks at this issue solely from a primary care perspective.

Linde et al performed a systematic review of treatments for depression, both both psychological and pharmacological, with one main stipulation - the participants "had to be recruited from a primary care setting." For clarity's sake, the authors divided their massive systematic review into 2 articles, one focusing on psychological treatments and one focusing on pharmacologic treatments.

In Effectiveness of Psychological Treatments for Depressive Disorders in Primary Care: Systematic Review and Meta-Analysis, the authors identified 30 studies that met inclusion criteria. There were several types of therapies in these studies: Cognitive Behavioral Therapy (CBT), "problem-solving" therapy, and/or "other face-to-face psychosocial therapies." The authors further grouped these studies by time spent between patient and therapist: face-to-face (at least 6 sessions), guided self-help (fewer than 6 face-to-face sessions), and no/minimal contact (less than 90 minutes of total face-to-face time). A handful of studies also investigated telephone counseling with either CBT or problem-solving therapy.

The authors found that all of these treatment modalities were more effective than usual care, though the effect size was greater for major depression diagnoses than for mild depression and/or dysthmia diagnoses. Interestingly, they also found that 6+ sessions of face-to-face counseling (regardless of the type of counseling) wasn't necessarily more effective than < 6 sessions and/or telephone counseling. For patients who find attending multiple counseling sessions burdensome, this meta-analysis shows that fewer sessions - or even telephone counseling - is just as effective.

In Effectiveness of Pharmacological Treatments for Depressive Disorders in Primary Care: Systematic Review and Meta-Analysis, the authors identified 66 studies that met inclusion criteria. Pharmacological treatments studied included multiple drug classes (TCAs, SSRIs, and several others). The authors found the most efficacy data for TCAs and SSRIs, though they found only "sparse" data on the "relative efficacy of anti-depressants" and could not make any determination regarding the superiority of any particular medications. They also found that TCAs are less acceptable to patients (higher rate of side effects leading to discontinuation) than SSRIs and the other newer classes of anti-depressants. The authors also commented that "there were no major differences in trials limited to patients with major depression and trials that included other depressive patients," which is helpful for family physicians who treat patients with less severe forms of depression.

Because this systematic review only included participants from a primary care setting, we can more comfortably generalize its findings to the patients we treat in our own offices. As family physicians, we need to be cautious about extrapolating too much from studies that focus on patients in a specialist's care population; by definition, these patients represent a narrower, often sicker population than the wider variety we see. This systematic review, sizable enough in scope to require 2 articles to fully describe its results, provides guidance for family physicians treating patients with mild to moderate depression as well as severe depression; it provides reassurance to patients unable to attend multiple psychotherapy sessions that even a few sessions can provide benefit. We need more studies like this one that report on participants from primary care settings.

There's an AFP By Topic on Depression and Bipolar Disorder if you'd like to read more; the collection contains articles about screening and diagnosis as well as treatment, and also has some helpful patient education materials.

Will this systematic review change the way you care for patients with depression?

Tuesday, February 17, 2015

Debating testosterone screening and therapy in older men

- Kenny Lin, MD, MPH

A good number of new patients to my practice are older men whose previous physicians have retired. More and more often, I've noticed while reviewing records from previous physicals that they have had their testosterone levels checked - usually without any documented rationale for doing so. In two Pro-Con editorials in the February 15th issue of American Family Physician, Drs. Joel Heidelbaugh and Adriane Fugh-Berman debate the merits and potential unintended consequences of screening for testosterone deficiency in older men. Dr. Heidelbaugh points out that observational studies have associated low serum testosterone levels with cardiovascular disease, cancer, impaired glucose tolerance, and metabolic syndrome. He further argues that symptoms of testosterone deficiency may be erroneously attributed to normal aging:

Although screening targets asymptomatic men, testosterone deficiency is unique because symptoms are not always well defined. This warrants casting a wider net to identify a treatable condition. Symptoms such as depression, fatigue, and inability to perform vigorous activity are related to low testosterone levels, whereas there is an inverse relationship between the number of sexual symptoms and testosterone levels.

On the other hand, Dr. Fugh-Berman raises concerns about overly aggressive marketing of testosterone supplements by pharmaceutical companies, such as online symptom surveys that seem designed to elicit "yes" answers from most older men.

These questions demonstrate how pharmaceutical companies use nonspecific symptoms to foster disease states and then convince physicians that these conditions are real. In this case, the disease state is marketed to consumers as Low T, and to physicians as late-onset hypogonadism.

Of observed associations between low testosterone levels and chronic diseases, Dr. Fugh-Berman counters that "association does not prove causation, and there is no reliable evidence that testosterone treatment improves any chronic disease."

Last September, an advisory committee to the U.S. Food and Drug Administration considered the potential cardiovascular risks for testosterone therapy and voted to exclude men with age-related testosterone declines from indications for testosterone use and to support performing additional studies to clarify cardiovascular harms. Whether clinical practice will evolve to reflect a similar level of caution is unclear. A 2013 analysis of a health insurance database showed that 25% of men prescribed a testosterone supplement never had a testosterone level checked, while other men with apparently normal levels nonetheless received therapy. At a minimum, family physicians who prescribe testosterone supplements should heed the Choosing Wisely recommendation to avoid these unsupported practices.

Monday, February 9, 2015

Effective vaccine counseling: ask, acknowledge, respond

- Jennifer Middleton, MD, MPH

The current U.S. measles outbreak has brought the complex issue of vaccine hesitancy back into the limelight. As of January 2015, 102 individuals in the U.S. contracted measles, along with 644 in 2014; this current outbreak seems to have originated at a Disney theme park in California, though the U.S. Centers for Disease Control and Prevention (CDC) has yet to identify the index case.

The CDC states that the "majority of the people who got measles were unvaccinated." Despite Dr. Andrew Wakefield's public shaming and a robust evidence base to the contrary, there are many Americans who believe that vaccines are unsafe.

It can be tempting to adopt a firm line with parents who refuse vaccinations for their child(ren); the American Academy of Pediatrics even has a vaccine refusal form physicians can have parents sign that outlines the risks of missed vaccinations. As physicians, we see the science in favor of vaccines along with the consequences of missed vaccines. We get frustrated at the inaccurate anti-vaccine information that can be found online. But if we channel that energy into using the same techniques we use to help our patients change other health-related behaviors, we just might increase vaccination rates.

For starters, it may help to remember that most parents want the best for their child(ren), as the authors of this 2011 Pediatrics article, Drs. Healy and Pickering, state:
Parents are attempting to make the best decisions on behalf of their children, a task made more difficult by many potentially conflicting sources of information. Parents may be more fearful of committing harm (giving an unsafe vaccine) than allowing harm (taking a chance that their child will develop a disease).
We need to ask parents about their worries, and acknowledge them, before responding with our expertise. Identifying parents' specific concern(s) allows physicians to appropriately target their counseling. Drs. Healy and Pickering identified the top three vaccine safety fears; for parents worried about autism (#1), we can describe the overwhelming evidence that vaccines do not cause autism. For parents worried about thimerosal, (#2) we can share that thimerosal is safe and also is rarely used in our current vaccines. For parents worried about immune system "overload" (#3), we can talk about how their child's immune system is capable of handling exponentially more antigens than vaccines will ever present. Targeting our counseling to parents' specific concerns may increase the likelihood of a decision to vaccinate.

A 2008 study found that the majority of parents who changed their mind about vaccination did so after obtaining additional information and/or "health assurances" about vaccine safety. Listening with genuine interest about why parents are worried about vaccination, and exploring these ideas with them in a non-judgmental way, may yield greater success than yielding to frustration. A parent-physician relationship grounded in trust also contributes to higher vaccination rates.

If you'd like to read more, there's an AFP By Topic on Immunizations (excluding Influenza) that includes links to patient information, Family Practice Management articles on increasing your office's vaccinations, and this AFP Journal Club discussing the evidence base behind the current measles vaccination recommendations.

What strategies are you using with vaccine-hesitant parents?

Monday, February 2, 2015

Once a Cesarean ... now, a vaginal delivery

- Kenny Lin, MD, MPH

AFP's February 1st issue featured a review article on counseling and complications of Cesarean delivery and a concise summary of the American Academy of Family Physicians' updated clinical practice guideline on planned vaginal birth after Cesarean (VBAC). The review article, authored by Drs. Jeffrey Quinlan and Neil Murphy, noted that Cesareans represent nearly one-third of all deliveries in the U.S., with the most common indications being elective repeat Cesarean delivery (30%) and dystocia or failure to progress (30%).

A recent essay in the "Narrative Matters" section of Health Affairs by physician and health policy researcher Carla Keirns highlighted the challenges that even a highly educated, well-informed patient faces in achieving the desired outcome of a vaginal childbirth, especially if her pregnancy is classified as high risk. Dr. Keirns, whose pregnancy was complicated by "advanced maternal age" (40) and gestational diabetes, narrowly avoided a Cesarean delivery by obstetricians who often seemed to be "watching the clock" more than assessing her individual circumstances. She observed how the "Cesarean culture" of medical practice overshadows the ideal of shared decision-making about delivery preference:

I was naked and uncomfortable, had invasive lines in place, and hadn’t slept or eaten in three days. If a doctor I trusted, instead of one I didn’t know, had suggested a cesarean forty-eight hours into my labor induction, I might have agreed. If they had told me that my baby’s life or health was in jeopardy, I would have consented to anything. The vision of the empowered consumer, or even the autonomous patient, is laughable under these circumstances.

Once a woman has had one Cesarean delivery, she faces considerable pressure from the medical system to choose repeat Cesarean deliveries in subsequent pregnancies. A 2014 article in The Atlantic explained why the dictum "once a Cesarean, always a Cesarean" increasingly holds true despite good evidence that planned VBAC is safe for, and desired by, most women. After the American College of Obsetricians and Gynecologists (ACOG) published guidelines in 1996 (later challenged by the AAFP) recommending that in-house surgical teams be "immediately available" during planned VBAC, many hospitals stopped allowing women to attempt labor after a Cesarean. Even though ACOG now acknowledges that there is no evidence that hospitals with fewer resources have worse maternal or neonatal outcomes from planned VBAC, these restrictive institutional policies have remained in place.

After our first child was born by Cesarean section, my wife, who is also a family physician. proceeded to have three consecutive uncomplicated vaginal deliveries after the age of 35. To change the culture of medicine to support this kind of outcome, and to reduce the overall frequency of Cesarean deliveries, patients, physicians, and hospitals must advocate for aligning medical protocols with the best evidence and putting mothers and babies back at the center of care.

Monday, January 26, 2015

Treating interstitial cystitis: pharmacologic and non-pharmacologic options

- Jennifer Middleton, MD, MPH

An estimated 4 million adults in the United States have interstitial cystitis (IC), a syndrome that can cause a variety of bothersome and uncomfortable urinary tract symptoms. The January 15 issue of AFP reviews the evidence base for treating IC; although researchers have yet to identify an effective long-term pharmacologic treatment, two short-term medication options exist with different effects on symptom scores.

This AFP FPIN Clinical Inquiry examined a systematic review from 2007 as well as a couple of more recent randomized controlled trials. The systematic review found heterogenity in study design and outcomes among included randomized controlled trials (RCTs), and the mean duration of these RCTs was only 15 weeks. The FPIN authors note that, in 6 studies, pentosan improved overall symptom scores ("better or worse than prior the intervention") but did not improve scores for specific symptoms like dysuria, urgency, or frequency.

Although the systematic review authors included a small 2001 RCT investigating cimetidine in their tables, they did not comment on it in their manuscript; the FPIN authors, however, had more interest in this study that randomized 36 participants to treatment with cimetidine versus placebo. Although the n is quite small, this RCT did show improvement in overall symptom scores as well as in the specific symptoms of nocturia and suprapubic pain.

Family physicians seeking to help their patients with IC may want to base their medication choice on each patient's symptoms. Although pentosan has been best studied for overall symptoms, cimetidine may be a useful alternative for patients whose predominant symptoms are nocturia and/or suprapubic pain.

Although the American Urological Association (AUA) recommends the use of amitriptyline for IC, the FPIN authors found conflicting evidence. While a smaller RCT (n = 50) showed benefit, a larger RCT (n = 271) did not. The AUA, however, lists all pharmacologic options for IC as second-line treatments, advising patient education, "self-care practices," "behavioral modification," and "stress management practices" as first-line treatments.

In line with those recommendations is a recent study that found a high rate of co-morbid mood symptoms in patients with IC. This 2015 study looked at the association between IC and symptoms of depression, anxiety, and/or insomnia; correlation does not necessarily equal causation, of course, and it's unclear if these symptoms co-exist with IC, predate IC, or come as a result of the frustrating symptoms of IC. Regardless, the hazard ratios (HR) for co-morbid depression, anxiety, or insomnia were 2.4, 2.4, and 2.1, respectively (all HRs had narrow 95th percentile confidence intervals). Although no studies to date have looked at mood treatments for IC, perhaps these studies are not far off given this association. In the meantime, family physicians can at least screen for and treat these co-morbid mood disorders.

If you'd like to read more, there's an AFP By Topic on Urinary Tract Infections/Dysuria that includes this 2011 AFP article on diagnosing and treating IC.

How do you care for patients with IC?

Wednesday, January 21, 2015

Are treatment recommendations for influenza evidence-based?

- Kenny Lin, MD, MPH

As the Centers for Disease Control and Prevention (CDC) reported that people who received this season's influenza vaccine were only 23 percent less likely to be diagnosed with influenza than unvaccinated persons, CDC director Tom Frieden was publicly urging high-risk patients and their physicians to use antiviral medications to prevent complications and disease transmission:

People who are sick with flu, if they're very sick in the hospital or if they have underlying, chronic medical conditions, like asthma, diabetes, heart disease, women who are pregnant, children under two and people over the age of 65 - all of these people, if they get flu, should get treated with antiviral drugs. The evidence indicates that it will shorten how long you're sick, might keep you out of the hospital and could even save your life. ... There is some evidence that suggests that taking antiviral medications may reduce the risk that you'll spread the disease to others in your family so it may be helpful for others as well as for yourself.

A previous AFP Community Blog post discussed a 2012 Cochrane review which cast doubt on the ability of the neuraminidase inhibitors oseltamivir and zanamivir to prevent influenza transmission, noting that after including data from unpublished, industry-sponsored, randomized controlled trials, the difference was not statistically significant.

Also in that year, a meta-analysis by AFP Deputy Editor Mark Ebell and colleagues concluded: "There is no evidence that oseltamivir reduces the likelihood of hospitalization, pneumonia or the combined outcome of pneumonia, otitis media and sinusitis." The authors noted that two large unpublished trials of oseltamivir in older persons and persons with chronic disease did not even show that the drug reduced the duration of symptoms, suggesting that oseltamivir might be less effective at treating influenza in high-risk groups.

In 2014, after gaining access to the complete clinical study reports from the manufacturers, the Cochrane Collaboration updated its previous review and drew the following conclusions: "Oseltamivir and zanamivir have small, non-specific effects on reducing the time to alleviation of influenza symptoms in adults, but not in asthmatic children." Taking either of the drugs did not reduce hospitalizations or serious complications, but did increase risk of nausea, headaches, and psychiatric symptoms. The CDC responded that their recommendations for antiviral medications "remained unchanged," arguing that observational studies not considered in the Cochrane review supported prescribing neuraminidase inhibitors for high-risk patients with influenza.

The bottom line for family physicians is that at best, antiviral medications for influenza have modest benefits that need to be balanced against potential adverse effects in deciding whom to treat. Also, existing evidence does not support the CDC's contention that antivirals are more likely to be beneficial in high-risk populations.