SSRIs Associated With Lower Bone Density in the Elderly
Approximately 62% of antidepressant prescriptions in the United States are for selective serotonin reuptake inhibitors (SSRIs), commonly used for the treatment of depression and often prescribed for the elderly. SSRIs inhibit a serotonin-transporting protein that may also be associated with an increased rate of bone loss in the elderly. Consequently, such increase in bone density can lead to greater risk of bone fractures.
Susan J. Diem, MD, MPH, at the University of Minnesota in Minneapolis, and colleagues, studied 2,722 female adults (average age=78.5 years) from 1997 through 1999. The study participants’ hip bone density and two subregions were measured during that period and approximately 5 years later. Participants were asked to bring to each visit any medications they had used in the last 2 weeks, including SSRIs and tricyclic antidepressant (TCAs).
The study found that 7.3% (198 participants) used SSRIs, 4.3% (118 participants) used TCAs, and 88.4% (2,406 paricipants) took neither type of antidepressant. Bone density at the hip decreased 0.82% in participants using SSRIs, even with adjustments for other factors that might affect bone density and antidepressant use such as severity of depression and use of calcium supplements. Participants who took TCAs or no antidepressants exhibited only a 0.47% decrease. Higher bone density rates in participants taking SSRIs were also found in the two hip subregions.
“We also observed that depression itself was associated with increased rates of bone loss, even after we excluded women taking antidepressants,” Dr. Diem said.
Based on data, it is theorized that SSRIs may interfere with the function of cells responsible for the regular breakdown and rebuilding of bones. However, further investigation is warranted.
“Due to limitations of the analysis, we cannot conclude based on our results that there is a cause and effect relationship between SSRI use and increased rates of bone loss,” said Dr. Diem. “It may be that other differences between SSRI users and non-users explain the association we observed between SSRI use and increased rates of bone loss.”
Dr. Diem added that the results suggest that clinicians should be aware that older women taking SSRIs may be at risk for higher rates of bone loss. However, she stressed that at this time patients should not stop taking their antidepressants based on these results.
Funding for this research was provided by the National Institutes of Health. (Arch Intern Med. 2007;167(12):1240-1245). —DC
Desvenlafaxine Succinate More Effective Than Placebo as Treatment for Major Depressive Disorder
Prior studies, including the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, have shown that patients with major depressive disorder (MDD) can achieve remission with ≥1 treatment steps. Desvenlafaxine succinate (DVS) is a serotonin and norepinephrine reuptake inhibitor (SNRI) currently in development for the treatment of menopausal vasomotor symptoms, fibromyalgia, and pain associated with diabetic neuropathy as well as MDD. Recently, researchers sought to determine the efficacy and safety of DVS solely for MDD treatment.
In the multicenter, randomized, double-blind, placebo-controlled, parallel-group, flexible-dose trial, Alan D. Feiger, MD, of the Feiger Health Research Center in Lakewood, Colorado, and colleagues, evaluated 235 outpatients taking either flexible doses of DVS 200–400 mg/day (n=117) or placebo over an 8-week period, which was followed by a 2-week tapering period. All patients were ≥18 years of age, met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for MDD, which was their primary diagnosis at the beginning of the study, and experienced MDD symptoms for ≥30 days prior to the first screening visit.
The primary study measure of medication efficacy was mean change in the 17-item Hamilton Rating Scale for Depression (HAM-D17) scores from baseline to final evaluation. Other efficacy measures included the Clinical Global Impressions Scale-Improvement (CGI-I) and Severity of Illness (CGI-S) scales, the visual analog scale-pain intensity (VAS-PI) overall pain score, and mean change in Montgomery and Asberg Depression Rating Scale (MADRS) score from baseline to final evaluation.
Feiger and colleagues found that there was no significant difference in HAM-D17 scores between the two treatment groups at the end of the study (mean change from baseline in the HAM-D17 total score was -7.48 in the placebo group and -9.08 in the DVS treatment group). The authors found a mean change in HAM-D17 scores at weeks 6 and 8 evaluations, but this finding was not shown at other assessment periods. In addition, there was no significant difference in VAS-PI scores between the two treatment groups.
Examining secondary outcome measures, Feiger and colleagues found that there was a significant difference between the treatment groups in MADRS, CGI-I, and CGI-S scores at the study end. Also, the authors said that DVS helped relieve some MDD symptoms, including depressed mood, anxiety, and other general somatic symptoms, and patients taking the medication showed a significant reduction in suicidal thoughts compared to patients who took placebo (Figure).
Treatment-emergent adverse events were consistent with other SNRIs and included nausea (36% of patients), dry mouth (31%), insomnia (28%), somnolence (23%), sweating (21%), anorexia (20%), tremor (11%), and impotence (16% of male patients). The authors concluded that, although the primary outcome measure did not show significant differences between the DVS and placebo treatment groups, observed case analyses and secondary outcome measures did show that DVS is an effective, safe, and well-tolerated treatment for MDD in adults.
Funding for this research was supported by Wyeth. (APA 2007, Poster NR 299.) —CP
Treatment for Depressive Disorders in Youths Declines After Advisory
In 2003, the United States Food and Drug Administration issued a public health advisory about the risk of suicide for children, adolescents, and young adult patients who take selective serotonin reuptake inhibitors (SSRIs) for the treatment of major depressive disorder (MDD). The advisory stated that there was not only an increased risk of suicide attempts for younger patients taking antidepressants, but there was also increased risk of suicidal ideation for children and adolescents.
Researchers at the University of Colorado at Denver and Health Sciences Center in Aurora recently investigated whether patterns of MDD diagnosis and prescriptions of antidepressants or pharmacologic alternatives to antidepressants as well as use of psychosocial care have changed after the FDA advisory was issued.
Led by Anne M. Libby, PhD, the authors created a large-scale national child, adolescent, and young adult cohort from the PharMetrics Patient-Centric Database, a national integrated claims database of managed care plans, in order to evaluate MDD treatment for this population. The PharMetrics Patient-Centric Database includes paid medical, specialty, facility, and pharmacy claims from >85 managed health care plans, which encompass four million members throughout the US.
Libby and colleagues evaluated a cohort of 65,349 patients 5–18 years of age with paid claims and who had been diagnosed with new MDD episodes from October 1998 to September 2005. The authors studied rates of MDD diagnosis and treatment trends for 2 years following the advisory and expected trends based on data from the 5 years preceding the advisory.
Libby and colleagues found that, from 1999 to 2004, diagnoses of MDD for children, adolescents, and young adults had steadily increased from 3 to 5 per 1,000 patients. However, 2 years after the advisory was released, the amount of MDD diagnosis decreased to the diagnostic rate in 1999. The authors said that this finding demonstrated a severe deviation from the earlier and historical trend. Separating the rates of new MDD diagnoses by gender, the authors found that past trends would have predicted that 6 per 1,000 female patients and 3.8 per 1,000 male patients were diagnosed with MDD. However, diagnostic rates showed that 2.3 per 1,000 male patients and 3.5 per 1,000 female patients were newly diagnosed with MDD.
Pediatricians and primary care physicians (PCPs) accounted for the largest reductions in new MDD diagnoses, and rates for the type of care provider diagnosing MDD in patients also changed. Twenty-four percent of new MDD diagnoses previously were made by PCPs and 22% were made by psychiatrists. The authors found that psychiatrists were making more new MDD diagnoses than PCPs based on predicted rates of diagnosis. PCPs were expected to make approximately 40% of diagnoses and made 27%, while psychiatrists were expected to make 20.4% of diagnoses and made 24.2%. The authors said this finding could be due to more PCPs referring young patients to psychiatrists for MDD diagnosis.
In addition, the proportion of MDD patients receiving no antidepressant increased to three times the rate predicted by the earlier trends. SSRI prescription fills were also 58% lower than predicted by trends.
“Among patients who were diagnosed, the proportion of cases that received antidepressants in the first 30 days was far lower than would have been expected based on the historical trend,” Dr. Libby said. “For those newly diagnosed pediatric patients, there was not strong evidence of other types of treatment to make up that gap, whether psychosocial services or other psychotropic medications.”
Libby added that while researchers expected antidepressant use to decline following the FDA advisory, they were most surprised by the reduction in diagnosis.
“This [reduction] reversed a national trend as evidence of a decade of work to educate and promote depression treatment in primary care,” Dr. Libby said. “Our concern is the lack of treatment for a disorder that is quite serious in childhood. As clinicians know, depression is a large and significant risk factor for suicide.”
Libby said that future studies will focus on the effects of the FDA advisory on adult depression treatment. (Am J Psychiatry. 2007;164(6):884-891.) —CP
Gender, Age, and Depressed State Impacts Patient Perspectives of Remission
Although cessation of symptoms for patients with major depressive disorder (MDD) is a common marker of remission (eg, as assessed by the Hamilton Rating Scale for Depression), remission is often perceived by patients based on other factors such as their age, gender, and depressed state.
Joseph B. McGlinchey, PhD, of the Department of Psychiatry and Human Behavior at Brown University School of Medicine in Providence, Rhode Island, and colleagues, surveyed 562 psychiatric outpatients with MDD at the Rhode Island Hospital Department of Psychiatry in Providence and assessed the importance of 16 remission factors. The sample included 191 (34%) males and 371 (66%) females 18–80 years of age (M=44.0, SD=11.7). Based on assessment using the Standardized Clinical Outcome Rating scale for Depression (SCOR-D), females were more likely than males to view emotional stabilization as important remission factors (Table). Older patients noted more remission factors than did younger patients. Level of depression did not affect patients’ ratings of remission factors.
The authors concluded that different perspectives of depression symptom remission were based on age and gender. A combination of a symptom-based approach to remission and psychosocial functioning should be evaluated as factors of remission for patients with depressive disorders. More studies on perspectives of remission in larger samples are warranted. (APA 2007, Poster NR 292). —DC
Posters were drawn from the 160th Annual Meeting of the APA (May 19–24, 2007, San Diego, California). Psychiatric Dispatches is written by Dena Croog and Carlos Perkins, Jr.