FDA Approves Desvenlafaxine Succinate for Treatment of Major Depressive Disorder

The United States Food and Drug Administration approved desvenlafaxine succinate (Pristiq, Wyeth Pharmaceuticals), a serotonin norepinephrine reuptake inhibitor, to treat adult patients with major depressive disorder (MDD). The recommended dosage for an adult with MDD is 50 mg/day. This dosage does not require titration, which allows patients to start immediately at the recommended dosage.

The efficacy of desvenlafaxine was established through four, 8-week randomized, double-blind, placebo-controlled, fixed-dose studies of adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for MDD. Approval was based on several post-marketing commitments, including conducting and submitting data from several studies—a new long-term maintenance relapse-prevention study; a sexual dysfunction study; a lower dosage study; pediatric studies and a non-clinical toxicity study.

The discontinuation rate due to adverse events for desvenlafaxine (4.1%) was similar to the rate for placebo (3.8%). The most common adverse events observed in MDD patients in fixed-dose, short-term studies were nausea, dizziness, insomnia, hyperhidrosis, constipation, somnolence, decreased appetite, anxiety, and specific male sexual function disorders.

For more information, please consult the medication’s full prescribing information (www.pristiq.com). –JC


Symptom Severity of Generalized Social Phobia Not Likely to Determine Success of Cognitive Behavioral Group Therapy

Primary care physicians may hesitate to refer an individual with severe generalized social phobia (GSP) for cognitive-behavioral group therapy (CBGT) because the patient may either not benefit from it or will stop treatment. Approximately 26% of patients who attend CBGT sessions do not complete treatment, and completers do not always show improvement. According to a study by Dave Davies, PhD, of the Royal Ottawa Mental Health Centre in Ontario, Canada, and colleagues, CBGT can benefit patients with GSP, but the severity of symptoms associated with GSP does not necessarily predict patient completion of or response to CBGT.

The 12-week study involved 78 patients between 18 and 61 years of age diagnosed with GSP in accordance with criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition–Text Revision and as assessed by the Social Phobia Diagnostic Questionnaire. Patients were randomly divided into groups of five to eight individuals, and each group attended 12 CBGT sessions hosted by two CBT-trained therapists. The program consisted of psycho-education, cognitive restructuring, within-session exposure, in vivo exposure homework, and relapse prevention. Using Social Phobia Inventory (SPIN) scores to determine response to treatment, 30 of the 51 participants who completed therapy (ie, attended ≥7 sessions and completed follow-up surveys) positively responded with a reduction of ≥9 points on the SPIN. Completers demonstrated a substantial decrease in social anxiety, avoidance, and cognitions. Their scores on both the Beck Anxiety Inventory and Beck Depression Inventory-II declined as well. Results suggest that CBGT can reduce social anxiety symptomatology among a majority of individuals with GSP, but they do not necessarily indicate symptom severity as a factor for determining completion of CBGT.

In addition, the researchers unexpectedly found that anxiety and associated avoidance were not the primary reasons for participants’ discontinuation of CBGT.

“[Participants] who completed therapy were not different from their counterparts who discontinued treatment in terms of any anxiety-related variables (eg, symptom severity, avoidance, strength of negative cognitions, and depression) assessed prior to treatment,” Dr. Davies said.

That the research primarily focuses on social anxiety symptomatology before and immediately after group treatment limits the study, as whether or not treatment responses are consistent in the long-term is not assessed. Lack of follow-up with participants who did not complete therapy limits the study as well, leaving the reason for patient discontinuation unknown.

“Ascertaining reasons for discontinuing would be helpful for planning future interventions that would increase retention of participants,” Dr. Davies said. (2008 ADAA, Poster 122). –ML


Increased Prevalence of Anxiety and Internalizing Problems in Children with OCD and Comorbid Depression

In adults, depressive and anxiety disorders often occur as comorbid conditions with obsessive-compulsive disorder (OCD). Studies have shown that approximately 33% of patients with OCD report comorbid depression, which has also been shown to negatively affect overall treatment response. Although researchers have investigated the efficacy of pharmacologic indications for the treatment of OCD and depression in children, few studies examine the prevalence of comorbid depression in children and adolescents with OCD. Research is also lacking in determining possible risk factors for comorbid depression in children and adolescents with OCD.

Kristin E. Canavera, MS, at the Virginia Polytechnic Institute and State University in Blacksburg, and colleagues, evaluated 56 children and adolescents with OCD to determine the prevalence and potential risk factors for comorbid depression. They hypothesized that comorbid depression in patients with OCD may be correlated with the comorbidity of other anxiety disorders, more severe symptomology, and presence of parental depression. They also sought to extend current understanding of comorbid OCD and depression in adults to the child and adolescent population.

Patients were 10–17 years of age (mean age=14.5 years). All participating families received the Anxiety Disorders Interview Schedule, which assessed symptoms of anxiety and depression. Patients were divided into two groups, ie, those who met diagnostic criteria for OCD and did not have comorbid depression (n=28), and those with OCD and a comorbid depressive disorder (n=28). The prevalence, severity, and risk of comorbid depression among patients in the study were measured using the Children’s Depression Inventory, the Penn State Worry Questionnaire for Children (PSWQ-C), and the 39-item Multidimensional Anxiety Scale for Children (MASC). Parental self-reports including the Child Behavior Checklist (CBCL) and the Depression, Anxiety, and Stress Scales were also used to determine depression rates for both children and parents.

Canavera and colleagues found that among children and adolescents with OCD, there were significant differences in symptomology for those with and without comorbid depression. Patients with OCD and comorbid depression showed significantly higher rates of pervasive worry (PSWQ-C score of 38.1 for OCD patients with depression compared to 28.6 for those without depression) and internalizing problems, as measured by the CBCL, than patients without comorbid depression. Anxiety disorders, including social anxiety disorder and generalized anxiety disorder, were commonly associated with presence of OCD with comorbid depression. Although differences in MASC and clinical severity were not significant, differences were present among patients with and without comorbid depression. Contrary to their hypotheses, the authors found that OCD severity was not significantly higher for children and adolescents with comorbid depression, and that mothers’ rates of depression and anxiety were not significantly higher for patients with comorbid depression.

These results show that children and adolescents with OCD and comorbid depression may experience more internalizing problems than those without depression, which may alter the treatment course to include both OCD and depressive symptoms. Although cognitive-behavioral therapy (CBT) has shown to be effective for adults with OCD and depression, the authors suggest that a CBT approach that includes family support may be more effective with children and adolescents. The authors recommend that future research investigate whether comorbid depression is related to specific obsessive or compulsive symptoms of OCD. (2008 ADAA, Poster 72). –CP


PCMAD: A Self-Report Scale for Improved Detection of Mood and Anxiety Disorders

Unrecognized or misdiagnosed mood and anxiety disorders have a taxing effect on the social and economic well being of society. Such strains may be reduced by heightened vigilance and improved detection of mood/anxiety disorders by primary care physicians (PCPs), but all private practices have limited resources, and, certainly, limited time to interact with patients directly.

Monica Vermani, BSc, MA, PsyD, at the START Clinic in Toronto, Canada, and colleagues, assessed the need for and created a self-report measure for diagnosing mood disorders.
“Our goal was to develop a psychometric screening tool that was self report driven and could allow for a primary care practitioner to identify earlier, patients in their clinic, who suffer from an anxiety disorder, major depressive disorder, or bipolar disorder,” Dr. Vermani said.

The Primary Care Mood and Anxiety Diagnoser (PCMAD) was devised to facilitate diagnosis and enhance proper communication of one’s symptoms, with the intention of recognizing psychological causes for physical symptoms patients suffer from. In turn, this would facilitate patients to receive appropriate treatment care and reduce unnecessary physician/lab visits. PCMAD is a 38-item, self-report measure designed as a sensitive assessment tool for the presence of mood and anxiety disorders, with a high positive predictive value to enhance PCPs’ ability to detect features that correlate with the presence of various anxiety and mood disorders. PCMAD was developed from questions in 10 existing psychometric scales, including the Beck Depression Inventory and the Mood Disorder Questionnaire.

To evaluate the clinical accuracy of PCMAD, Vermani and colleagues administered the Mini-International Neuropsychiatric Interview (MINI) to 1,007 recruits in Phase I. From the MINI results, the investigators gauged the presence of generalized anxiety disorder (GAD), panic disorder, social anxiety disorder (SAD), bipolar disorder, and major depressive disorder (MDD). Subjects who demonstrated the presence of a mood and/or anxiety disorder(s) after the MINI were permitted into Phase II, in which the PCMAD was administered. Phase III included a patient’s chart review to determine whether each patient had a record of the mood disorder(s) detected during Phases I and II. Finally, in Phase IV, PCPs were asked to administer a clinical questionnaire pertaining to the specific subject.

When examining the outcome diagnoses after Phase IV, percentages of subjects with a mood/anxiety disorder(s) not detected by PCPs were as follows: 51.1% of patients with MDD, 87.4% with bipolar disorder, 62.2% with GAD, 73.6% with panic disorder, and 97.1% with SAD.

“A variety of factors contribute to the difficulty that physicians had in detecting these illnesses in their patients,” Dr. Vermani said. “Specifically, the constraints included time limited medical appointments, in sufficient resources and poor communication of physical/psychological symptoms and significant life stressors or life altering events by the patient."

According to the authors, PCMAD will promote communication between doctors and patients, leading the way to uncover symptoms that appear to be physical but are sometimes psychologically based, decreasing the occurrence of repeated physician visits and enhancing patients’ quality of life.

“Overall,” Dr. Vermani said, “since majority of the population with mood and anxiety disorders are likely to visit their primary care physician, it is crucial to enhance detection in order to minimize individual, economic, medical and societal costs incurred by such illnesses.”

It is Vermani and colleagues’ hope that the self administered psychometric screener they are developing will allow PCPs to go beyond examining a patient’s physical symptoms and seek for psychological triggers and stressful life events eliciting physical responses.

“This will hopefully allow for earlier detection, mis/overuse of medical services, earlier provision of treatments, and an overall decrease in patient sufferings,” Dr. Vermani said.

Funding for this study was provided by an unrestricted educational grant from Wyeth Canada (Poster presented at the 2008 ADAA). –LS


Increased Cell Phone Use May Heighten Symptoms of Anxiety

Cell phones and other handheld communication devices allow people to contact each other more easily and more often. However, such communication facility may cause people to feel obligated to remain connected and available to others. A study by Lisa Merlo, PhD, and Amanda Stone of the University of Florida in Gainesville, FL, found that individuals with higher levels of trait anxiety likewise have higher levels of cell phone abuse and dependence.

This preliminary investigation involved 183 individuals between 18 and 75 years of age from diverse backgrounds (approximately 76% Caucasian, 10% Asian, 9% Latino, 2% African-American, and 3% “other”). The participants owned a cell phone for an average of 7.2 years and were evaluated using three measures, ie, Cellular Technologies Addiction Scale (CTAS), State-Trait Anxiety Inventory (STAI), and International Personality Item Pool (IPIP-NEO). The CTAS consisted of two subscale questionnaires that gauged cell phone dependence and abuse. The Trait Anxiety subscale of the STAI assessed trait anxiety symptoms, and the Anxiety subscale of the IPIP-NEO measured anxiety. The negative correlation between age and the scores on the CTAS Abuse and Dependency scales suggest that cell phone addiction symptoms are more common in the younger participants regardless of gender. Scores on the STAI-Trait Anxiety scale were highly correlated with scores on the IPIP-NEO Anxiety scale, providing evidence of the association between anxiety symptoms and increased obstructive cell phone use.

The most interesting finding from this study was participant response to the CTAS Dependence subscale item, “I sometimes think that I might be ‘addicted’ to my cell phone.” Approximately 18% (one in five) of individuals admitted that they somewhat or strongly agreed.

“Though cell phone addiction has become a more prominent topic in pop culture, I was surprised that such a large number endorsed feeling this way,” Dr. Merlo said. “It appears that this may be a more prevalent issue than I initially thought.”

Due to the relatively small sample of healthy volunteers, research was unable to assess whether symptoms of cell phone addiction are more common among people with diagnosable anxiety disorder, especially in consideration of race and gender. In addition, whether individuals who manage anxiety disorders well report fewer symptoms of cell phone addiction than individuals who poorly manage anxiety disorders was not addressed.

Despite limitations, the study suggests that excessive cell phone usage may reflect maladaptive attempts at coping, especially among patients with high anxiety.

“Primary care physicians may wish to ask patients about cell phone usage, particularly about ways that cell phone usage may cause distress, impairment, or other negative consequences,” Dr. Merlo said. “Individuals who endorse significant problems would likely benefit from a referral to a mental health professional in order to learn more adaptive coping strategies.” (2008 ADAA, Poster 123). –ML


Environmental Cues and Rituals Often Trigger Hairpulling for Patients with Focused-Type Trichotillomania

Classified as an impulse-control disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, trichotillomania has also been classified as a stress and tension-releasing habit disorder as well as a variant of obsessive-compulsive disorder (OCD), which has led to debate as to the conceptualization of the hairpulling disorder. Research has shown that trichotillomania occurs on a continuum of two types, automatic and focused hairpulling, which each highlight different aspects of the disorder’s varied classifications. While automatic hairpulling occurs when the patient is unaware of the behavior (eg, occurring during other activities, such as reading or watching television), focused hairpulling is caused by intense urges to perform the behavior and satisfaction when the behavior is being performed, which is more representative of the diagnostic criteria for the disorder.

For both forms of trichotillomania, cues associated with the hairpulling are important to identify in order to begin effective treatment and optimize outcomes. Rebecca Nichols at the University of Florida in Gainesville, and colleagues, sought to investigate hairpulling symptoms in a non-clinical population of 527 people to examine the phenomenology of trichotillomania among different populations because such understanding would benefit clinicians in the recognition and treatment of trichotillomania.

Study participants were assessed for presence of trichotillomania using the two-part Florida Hairpulling Scale, which includes the qualitative and quantitative assessment of hairpulling cues and six questions related to the type and severity of hairpulling behavior. Researchers found that among the 527 study participants, between 17–47 years of age, 0.74% engaged in hairpulling behavior with the age of trichotillomania onset being 13.57 years. Among participants with trichotillomania, 80.4% were female and 19.6% were male; 68.7% engaged in automatic hairpulling while 31.3% exhibited focused hairpulling behavior.

Nichols and colleagues compared rituals associated with hairpulling among those who engaged in automatic and focused types of the behavior. They found that participants who were in the focused hairpulling group had a greater frequency of rituals associated with the behavior (56.3% for the focused group, 20% for the automatic group). Rituals included pulling hair from the root, examining the hair root, using certain fingers to pull hair, and dropping hair to the floor.

In addition, those in the focused group reported engaging in hairpulling behavior in more environments than those in the automatic group. Environmental cues included “reading,” “lying in bed,” “looking in the mirror,” “when alone,” and “watching television.” Overall, participants in the focused group reported more rituals and environmental cues triggered hairpulling behavior. The authors concluded that people who engage in focused hairpulling view the activity as a target of their attention, leading to more severe incidence. They added that these results show that there is a difference between focused and automatic hairpulling among those with trichotillomania, and may indicate the differences among current classifications for the disorder with focused hairpulling representing a more severe subtype of the condition. (2008 ADAA, Poster 85). –CP


Biologic Factors May Play a Role in the Development of Eating Disorders in Females

Eating disorders, exhibited mostly in females, are often attributed to environmental factors such as thinness ideals. However, a new study suggests that biologic factors may play a role as well. Kristen Culbert, MA, at Michigan State University in East Lansing, and colleagues, studied the effects of testosterone in twin pairs enrolled at the Michigan State University Twin Registry. The study found that females who were in the womb with a male twin have a lower risk for eating disorders than those with a female twin.

The study consisted of 304 same-sex female twins, 59 opposite-sex female twins, 54 opposite-sex male twins, and 165 same-sex male twins. Levels of disordered eating were measured by the Minnesota Eating Behavior Survey, which measures body dissatisfaction, preoccupation with weight, binge eating, and behaviors to control weight such as purging. As hypothesized, linear trends of disordered eating were found. Same-sex female twins exhibited the highest level of disordered eating, followed by opposite-sex female twins, opposite-sex male twins, and same-sex male twins. This trend was not accounted for by anxiety levels or social factors.

“Given that sociocultural differences, such as pressures for thinness in women, have typically been used to explain sex differences in eating disorder prevalence, findings from this study are most interesting in suggesting a biological explanation,” Culbert said. “Specifically, our findings provide evidence that increased levels of prenatal testosterone exposure may protect against the development of disordered eating attitudes and behaviors.”

The findings also ruled out socialization effects of being reared with a brother. Opposite-sex female twins exhibited lower (ie, more male-like) levels of disordered eating than non-twin females with at least one brother.

As the twins with the most male exposure in the womb were less likely to develop disordered eating, the authors concluded that biologic factors such as masculinization of the central nervous system by prenatal exposure to testosterone may affect the prevalence of disordered eating. Culbert said that in the long term, the identification of neurobiologic processes underlying risk for eating disorders might enhance treatment.

“If prenatal testosterone is protective and acts to organize anatomical and functional brain differences between males and females, then we can begin to identify areas of the brain that might be altered by prenatal testosterone, such as those involved in food intake or satiation,” Culbert said. “This information would be important for understanding how prenatal testosterone confers protection against disordered eating and could ultimately be used to develop new pharmacological treatments that could mimic these protective effects.”

The practical application of this study is that healthcare professionals can help to reduce parental or personal guilt by highlighting that eating disorders are biologically based and that the risk for eating disorders results from socio-cultural and familial factors that act in combination with biologic and genetic vulnerabilities.

The biggest limitation to this study was the inability to directly assess levels of prenatal testosterone exposure. Additional research examining more direct assessments of prenatal testosterone exposure is warranted. However, at present, only prohibitively invasive methods, such as amniocentesis, exist.

“While such methods would be invaluable for directly examining levels of prenatal testosterone exposure, researchers are limited by the lack of access to and difficulties collecting these data,” Culbert said.

Funding for this study was provided by the National Institute of Mental Health. (Arch Gen Psychiatry. 2008;65(3):329-336). –DC


First-Trimester Maternal Stress During Pregnancy Linked to Later-Life Schizophrenia in Offspring

During pregnancy, an elaborate biologic system protects fetuses from the physiologic effects of maternal stress during crucial neurodevelopment—particularly during the first trimester. That system, known as a “fetal-placental barrier,” is hardly impenetrable, however, and a recent study reveals several fetal risk factors associated with antenatal maternal stress. The study weighed the claim that maternal stress during the first trimester of pregnancy was especially associated with the risk of congenital malformations.

Ali S. Khashan, MSc, of the Centre for Women’s Mental Health Research at the University of Manchester, and colleagues, compiled data from several national databases in Denmark. In a cohort of 1.38 million Danish births, born between the years of 1973 and 1995, mothers were considered exposed to stress if ≥1 close relatives died or were diagnosed with cancer, acute myocardial infarction, or stroke syndrome either 6 months before conception or during pregnancy. The offspring were tracked from 10 years of age until their death, migration, or onset of schizophrenia, or until June 2005. Maternal relatives were also tracked for outcomes including death, serious illness, or terminal diagnoses. Of the 1.38 million births included in this investigation, the mothers of 36,193 offspring were exposed to the death, serious illness, or terminal diagnosis of a close relative, of which 21,987 mothers were exposed to the death of a family member. Finally, 14,206 mothers were exposed to a relative with serious illness.

These birth records were compared with psychiatric inpatient and outpatient data in order to assess the relationship between maternal exposure to severe stress and adverse mental health outcomes in their offspring. The most significant finding was that the offspring of mothers who were exposed to the death of a close relative during the first trimester were more likely to develop schizophrenia later in life (adjusted relative risk=1.67 [95% CI]). This increased risk was not associated with maternal stress during the 6 months preceding conception or during other trimesters.

Funding for this study was provided by Tommy’s The Baby Charity and the Stanley Medical Research Institute. (Arch Gen Psychiatry. 2008;65(2):146–152). –LS

Posters were drawn from the 28th Annual Conference of the Anxiety Disorders Association of America (ADAA; March 6–9, Savannah, Georgia). Psychiatric dispatches is written by Dena Croog, Jaime Cunningham, Michelisa Lanche, Carlos Perkins, Jr., and Lonnie Stoltzfoos.