A Double-Masked, Placebo-Controlled Study of Fluoxetine for Hypochondriasis

This study assessed the efficacy, durability, and tolerability of fluoxetine for hypochondriasis, a disorder for which controlled pharmacological trials are scarce. Fifty-seven patients with hypochondriasis were enrolled: 12 discontinued during the placebo run-in, and 45 were randomized to either fluoxetine or placebo for 12 weeks (acute treatment). Responder status was defined as a Clinical Global Impression rating for hypochondriasis of much or very much improved. Secondary outcome measures included severity of hypochondriasis, somatization, anxiety, and depression. Responders to acute treatment entered a 12-week maintenance phase to week 24. Sustained responders at week 24 entered a 12-week double-masked discontinuation phase. Primary analysis used the intent-to-treat sample. More patients responded with improvement in hypochondriasis when given fluoxetine compared with placebo, starting at week 8 (50.0% vs 19.0%, P = 0.03) and continuing to week 12 (62.5% vs 33.3%, P = 0.05). Mean dose at week 12 dose was 51.4 mg (SD, T23 mg). The acute treatment response was maintained to week 24 with more responders in the fluoxetine compared with the placebo group (54.2% vs 23.8%, P = 0.04). Significant improvement was not noted on the continuous secondary outcomes measures of hypochondriasis, with the exception of the Clinical Global Impression hypochondriasis severity scale at week 24. Likelihood of response was not associated with severity of psychiatric comorbidity. Durability of response after controlled drug discontinuation could not be reasonably assessed, given the small sample size of patients who entered the discontinuation phase (n = 10). Fluoxetine was well tolerated, with no significant differences in discontinuation due to side effects between treatment groups. Fluoxetine is a moderately effective and well-tolerated treatment for hypochondriasis

The impact of losing a child on the clinical presentation of complicated grief

BackgroundIt is unclear whether bereaved parents with Complicated Grief (CG) struggle with their grief differently than others with CG. This study addressed this question by comparing CG severity, CG-related symptoms, thoughts and behaviors, and comorbid psychiatric diagnoses of bereaved parents with CG to the diagnoses and symptoms of others with CG.MethodsBaseline data from 345 participants enrolled in the Healing Emotions After Loss (HEAL) study, a multi-site CG treatment study, were used to compare parents with CG (n=75) to others with CG (n=275). Data from the parent group was then used to compare parents with CG who had lost a younger child (n=24) to parents with CG who had lost an older child (n=34). Demographic and loss-related data were also gathered and used to control for confounders between groups.ResultsParents with CG demonstrated slightly higher levels of CG (p=0.025), caregiver self-blame (p=0.007), and suicidality (p=0.025) than non-parents with CG. Parents who had lost younger children were more likely to have had a wish to be dead since the loss than parents who had lost older children (p=0.041).LimitationsAll data were gathered from a treatment research study, limiting the generalizability of these results. No corrections were made for multiple comparisons. The comparison of parents who lost younger children to parents who lost older children was limited by a small sample size.ConclusionsEven in the context of CG, the relationship to the deceased may have a bearing on the degree and severity of grief symptoms and associated features. Bereaved parents with CG reported more intense CG, self-blame, and suicidality than other bereaved groups with CG, though this finding requires confirmation. The heightened levels of suicidal ideation experienced by parents with CG, especially after losing a younger child, suggest the value of routinely screening for suicidal thoughts and behaviors in this group

Optimizing Treatment of Complicated Grief: A Randomized Clinical Trial

ImportanceTo our knowledge, this is the first placebo-controlled randomized clinical trial to evaluate the efficacy of antidepressant pharmacotherapy, with and without complicated grief psychotherapy, in the treatment of complicated grief.ObjectiveTo confirm the efficacy of a targeted complicated grief treatment (CGT), determine whether citalopram (CIT) enhances CGT outcome, and examine CIT efficacy without CGT.Design, setting, and participantsIncluded in the study were 395 bereaved adults who met criteria for CG recruited from March 2010 to September 2014 from academic medical centers in Boston, Massachusetts; New York, New York; Pittsburgh, Pennsylvania; and San Diego, California. Co-occurring substance abuse, psychosis, mania, and cognitive impairment were exclusionary. Study participants were randomized using site-specific permuted blocks stratified by major depression into groups prescribed CIT (n = 101), placebo (PLA; n = 99), CGT with CIT (n = 99), and CGT with PLA (n = 96). Independent evaluators conducted monthly assessments for 20 weeks. Response rates were compared under the intention-to-treat principle, including all randomized participants in a logistic regression with inverse probability weighting.InterventionsAll participants received protocolized pharmacotherapy optimized by flexible dosing, psychoeducation, grief monitoring, and encouragement to engage in activities. Half were also randomized to receive manualized CGT in 16 concurrent weekly sessions.Main outcomes and measuresComplicated grief-anchored Clinical Global Impression scale measurments every 4 weeks. Response was measured as a rating of "much improved" or "very much improved."ResultsOf the 395 study participants, 308 (78.0%) were female and 325 (82.3%) were white. Participants' response to CGT with PLA vs PLA (82.5% vs 54.8%; relative risk [RR], 1.51; 95% CI, 1.16-1.95; P = .002; number needed to treat [NNT], 3.6) suggested the efficacy of CGT, and the addition of CIT did not significantly improve CGT outcome (CGT with CIT vs CGT with PLA: 83.7% vs 82.5%; RR, 1.01; 95% CI, 0.88-1.17; P = .84; NNT, 84). However, depressive symptoms decreased significantly more when CIT was added to treatment (CGT with CIT vs CGT with PLA: model-based adjusted mean [standard error] difference, -2.06 [1.00]; 95% CI, -4.02 to -0.11; P = .04). By contrast, adding CGT improved CIT outcome (CIT vs CGT with CIT: 69.3% vs 83.7%; RR, 1.21; 95% CI, 1.00-1.46; P = .05; NNT, 6.9). Last, participant response to CIT was not significantly different from PLA at week 12 (45.9% vs 37.9%; RR, 1.21; 95% CI, 0.82-1.81; P = .35; NNT, 12.4) or at week 20 (69.3% vs 54.8%; RR, 1.26; 95% CI, 0.95-1.68; P = .11; NNT, 6.9). Rates of suicidal ideation diminished to a substantially greater extent among participants receiving CGT than among those who did not.Conclusions and relevanceComplicated grief treatment is the treatment of choice for CG, and the addition of CIT optimizes the treatment of co-occurring depressive symptoms.Trial registrationclinicaltrials.gov Identifier: NCT01179568

Prolonged grief disorder: clinical utility of ICD-11 diagnostic guidelines

BACKGROUND: The World Health Organization (WHO) International Classification of Disease (ICD-11) is expected to include a new diagnosis for prolonged grief disorder (ICD-11PGD). This study examines the validity and clinical utility of the ICD-11PGD guideline by testing its performance in a well-characterized clinical sample and contrasting it with a very different criteria set with the same name (PGDPLOS). METHODS: We examined data from 261 treatment-seeking participants in the National Institute of Mental Health (NIMH)-sponsored multicenter clinical trial to determine the rates of diagnosis using the ICD-11PGD guideline and compared these with diagnosis using PGDPLOS criteria. RESULTS: The ICD-11PGD guideline identified 95.8% [95% confidence interval (CI) 93.3-98.2%] of a treatment-responsive cohort of patients with distressing and impairing grief. PGDPLOS criteria identified only 59.0% (95% CI 53.0-65.0%) and were more likely to omit those who lost someone other than a spouse, were currently married, bereaved by violent means, or not diagnosed with co-occurring depression. Those not diagnosed by PGDPLOS criteria showed the same rate of treatment response as those who were diagnosed. CONCLUSIONS: The ICD-11PGD diagnostic guideline showed good performance characteristics in this sample, while PGDPLOS criteria did not. Limitations of the research sample used to derive PGDPLOS criteria may partly explain their poor performance in a more diverse clinical sample. Clinicians and researchers need to be aware of the important difference between these two identically named diagnostic methods

Treatment Expectancy and Working Alliance in Pharmacotherapy as Predictors of Outcomes in Complicated Grief

ObjectiveNonspecific factors, such as treatment outcome expectancy and working alliance, can influence treatment outcome. No studies to date have examined the role of expectancy and alliance on pharmacotherapy outcomes in individuals with complicated grief (CG).MethodThis secondary analysis of a larger randomized, control trial (RCT) examined the relationship between pharmacotherapy expectancy and alliance on treatment outcome in adults with CG who were participating in a multisite, double-blind, RCT examining the efficacy of citalopram and complicated grief treatment (CGT). Participants (n = 202) were randomized to one of four treatment conditions: citalopram (CIT), placebo (PBO), CGT + citalopram (CGT + CIT), or CGT + placebo (CGT + PBO).ResultsPharmacotherapy outcome expectancy and working alliance were higher among individuals randomized to CGT + CIT and CGT + PBO compared with CIT or PBO without CGT. Pharmacotherapy outcome expectancy was higher at Week 2 among individuals who ultimately responded to treatment compared with those who did not and among those who remained in treatment compared with those who dropped out. In contrast, working alliance did not correlate with dropout or treatment outcomes in pharmacotherapy.ConclusionsExpectancy for medication was higher among individuals randomized to receive CGT. Clinicians should assess symptoms and expectancies in the first weeks of treatment because these could be early markers of drop out and treatment response. (PsycINFO Database Recor

Treatment expectancy and working alliance in pharmacotherapy as predictors of outcomes in complicated grief.

ObjectiveNonspecific factors, such as treatment outcome expectancy and working alliance, can influence treatment outcome. No studies to date have examined the role of expectancy and alliance on pharmacotherapy outcomes in individuals with complicated grief (CG).MethodThis secondary analysis of a larger randomized, control trial (RCT) examined the relationship between pharmacotherapy expectancy and alliance on treatment outcome in adults with CG who were participating in a multisite, double-blind, RCT examining the efficacy of citalopram and complicated grief treatment (CGT). Participants (n = 202) were randomized to one of four treatment conditions: citalopram (CIT), placebo (PBO), CGT + citalopram (CGT + CIT), or CGT + placebo (CGT + PBO).ResultsPharmacotherapy outcome expectancy and working alliance were higher among individuals randomized to CGT + CIT and CGT + PBO compared with CIT or PBO without CGT. Pharmacotherapy outcome expectancy was higher at Week 2 among individuals who ultimately responded to treatment compared with those who did not and among those who remained in treatment compared with those who dropped out. In contrast, working alliance did not correlate with dropout or treatment outcomes in pharmacotherapy.ConclusionsExpectancy for medication was higher among individuals randomized to receive CGT. Clinicians should assess symptoms and expectancies in the first weeks of treatment because these could be early markers of drop out and treatment response. (PsycINFO Database Recor

Changes in typical beliefs in response to complicated grief treatment

BackgroundProlonged grief disorder (PGD) is a new diagnosis in the 11th edition of the International Classification of Diseases, estimated to affect 1 in 10 bereaved people and causing significant distress and impairment. Maladaptive thoughts play an important role in PGD. We have previously validated the typical beliefs questionnaire (TBQ), which contains five kinds of thinking commonly seen in PGD: protesting the death, negative thoughts about the world, needing the person, less grief is wrong, and grieving too much. The current paper examines the role of maladaptive cognition as measured by the TBQ in PGD and its change with treatment.MethodsAmong participants in a multisite clinical trial including 394 adults, we examined (a) the relationship between maladaptive thoughts at baseline and treatment outcomes, (b) the relationship between maladaptive thoughts and suicidality at baseline and posttreatment, and (c) the effect of treatment with and without complicated grief therapy (CGT) on maladaptive thinking.ResultsTBQ scores were associated with treatment outcomes and were strongly related to suicidal thinking before and after treatment. TBQ scores showed significantly greater reduction in participants who received CGT with citalopram versus citalopram alone (adjusted mean standard error [SE] difference, -2.45 [0.85]; p = .004) and those who received CGT with placebo versus placebo alone (adjusted mean [SE] difference, -3.44 [0.90]; p < .001).ConclusionsMaladaptive thoughts, as measured by the TBQ, have clinical and research significance for PGD and its treatment