A double-blind, placebo-controlled study of the impact of galantamine on anterograde memory impairment during electroconvulsive therapy.

BACKGROUND: Electroconvulsive therapy (ECT) continues to be an effective treatment option for patients who fail to respond to pharmacological interventions, are unable to tolerate medications, and show a suboptimal response to behavioral and psychotherapeutic treatments. However, risks for cognitive impairment may contribute to some patients' refusal of ECT. METHODS: The present study examined galantamine as a pharmacological intervention to reduce cognitive adverse effects from ECT. Thirty-nine inpatients diagnosed with major depressive disorder; bipolar disorder, depressed type; or schizoaffective disorder, depressed type and admitted for ECT were randomized to galantamine or placebo. Study drugs were initiated 24 to 48 hours before starting ECT and continued throughout the course of ECT. A neuropsychological test battery was administered at baseline and 24 to 48 hours after completing a course of ECT treatments. Depression severity was monitored using the 17-item Hamilton Rating Scale for Depression and Clinical Global Impression Scale at baseline, weekly, and end point. Self-rated adverse effects were monitored weekly. RESULTS: Thirty participants (12 patients in the galantamine group, 18 patients in the placebo group) had both pretreatment and posttreatment neuropsychological ratings. Those in the galantamine group scored significantly higher at discharge for delayed memory (t28 = 2.44, P < 0.05). Hierarchical regressions examined if treatment condition predicted changes in delayed memory scores from baseline to discharge. Inclusion of the treatment condition in the final model made a significant incremental improvement in prediction (ΔR = 0.12, F1,27 change = 4.65, P < 0.05; ß = 0.37, t = 2.16, P < 0.05). Galantamine was well tolerated with no clinically significant bradycardia or prolonged paralysis when administered with ECT. CONCLUSIONS: Galantamine may be protective against impairment in retention of new learning. Galantamine exhibited minimal adverse effects and was safe when administered during ECT. The present findings require replication by future researchers using larger samples before broad conclusions can be drawn.

Multimodal Imaging of West African Crystalline Maculopathy in an Igbo Man.

Purpose: This report describes a case of West African crystalline maculopathy. Methods: A case report is presented. Results: A 71-year-old Nigerian man was referred for evaluation of bilateral crystalline retinal deposits seen on routine examination. The patient had no acute visual symptoms and no significant ocular history except for cataract extraction and intraocular lens implantation in both eyes. Dilated fundocscopic examination was notable for bilateral greenish-yellow, foveocentric intraretinal crystalline deposits, which were visible on color fundus photography, multicolor confocal scanning laser ophthalmoscopy, and spectral-domain optical coherance tomography. The crystalline deposits were not associated with abnormal short-wavelength autofluorescence or fluorescein angiography findings. Conclusions: A diagnosis of West African crystalline maculopathy was made after other causes of crystalline maculopathy were excluded.

Multimodal imaging of type 2 acute macular neuroretinopathy in a young woman.

We report a case of type 2 acute macular neuroretinopathy (AMN) that occurred in an otherwise healthy 22-year-old white woman taking oral contraceptives and consuming large quantities of caffeinated coffee. The patient presented with a teardrop-shaped scotoma just inferior to her central vision in her left eye after a recent and significant increase in coffee consumption. A small extrafoveal retinal lesion was present superior to the fovea on pseudocolor fundus photography. Multimodal retinal imaging demonstrated focal disruption of the inner segment-outer segment junction of the photoreceptors with overlying hyperreflectivity at the level of the outer plexiform layer superior to the fovea, consistent with a diagnosis of type 2 AMN. Oral contraceptive use and high caffeine intake may be risk factors for the development of type 2 AMN.

Psychoticism and paranoid ideation in patients with nonpsychotic major depressive disorder: prevalence, response to treatment, and impact on short- and long-term treatment outcome.

UNLABELLED: Objective/Introduction: We sought to characterize the impact of the 90-item Symptom Checklist (SCL-90) subscales for paranoid ideation (PI) and psychoticism (P) in patients with major depressive disorder (MDD), on acute antidepressant response and on relapse prevention. METHODS: Subjects with Structured Clinical Interview for DSM Disorders-diagnosed nonpsychotic MDD were recruited into a clinical trial of open-label fluoxetine 10-60 mg/day for 12 weeks, followed by double-blind randomization of responders (n=262) to fluoxetine continuation or placebo for 12 months. PI and P were assessed with the patient-rated SCL-90. The association of these symptoms with response to treatment was assessed by logistic regression. RESULTS: We found significant decreases in PI and P during acute treatment phase for fluoxetine responders and nonresponders, although only 10.3% and 7.5% of patients experienced a >50% reduction in PI and P scores, respectively. Neither PI nor P scores significantly predicted time to relapse. P scores predicted a lower response rate to treatment with fluoxetine. DISCUSSION: The results of the present study suggest that there is a significant relationship between the presence of psychoticism in patients with nonpsychotic MDD, and the likelihood of overall depressive symptom improvement following a trial of monotherapy with fluoxetine. CONCLUSION: An increased burden of psychoticism in depressed subjects may confer poorer response to fluoxetine, but not increased risk of relapse among fluoxetine responders.

An open study of aripiprazole and escitalopram for psychotic major depressive disorder.

OBJECTIVE: This 7-week trial assessed the efficacy and tolerability of aripiprazole combined with escitalopram in the acute treatment of major depressive disorder, with psychotic features (MD-Psy). METHODS: Sixteen male and female patients with a Diagnostic Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of MD-Psy were recruited for this study from September 13, 2004 to August 9, 2006. Escitalopram and aripiprazole were flexibly dosed for 7 weeks, with maximum dosages of 20 and 30 mg/d, respectively. The 17-item Hamilton Rating Scale for Depression (HAM-D-17) and Structured Clinical Interview for DSM-IV psychosis module were used to measure depression and psychosis responses. The Barnes Akathisia Scale and the Simpson Angus Scale were used to assess for akathisia and extrapyramidal symptoms. RESULTS: Thirteen of the 16 subjects completed the study. The MD-Psy response rate (50% or greater drop in HAM-D-17 and no psychosis) (intent-to-treat, last observation carried forward) was 62.5%, and the MD-Psy remission rate (HAM-D-17, <8, and no psychosis) (intent-to-treat, last observation carried forward) was 50.0%. Ten of the 16 subjects developed akathisia; however, 9 of the 10 subjects had resolution or partial resolution of akathisia with dose adjustment or treatment with propranolol. CONCLUSIONS: The combination of escitalopram and aripiprazole seems to be an effective and safe treatment for MD-Psy.

The response of psychotic-like symptoms to fluoxetine monotherapy in non-psychotic major depressive disorder.

OBJECTIVE: To determine the prevalence of psychotic-like symptoms in non-psychotic major depressive disorder and to monitor the response of these symptoms to monotherapy with fluoxetine. METHODS: We reviewed the charts of 384 subjects (54.7% women; mean age 39.9±10), all outpatients diagnosed with non-psychotic major depressive disorder by the Structured Clinical Interview for DSM-IV (SCID), aged 18-65 years, with an initial 17-item Hamilton Depression (HAM-D-17) score of 16 or greater. Subjects were treated openly with fluoxetine 20 mg/day for 8 weeks. Subjects were administered the SCID-II (Structured Clinical Diagnostic Interview for Personality Disorder) prior to entering acute treatment and at the completion of the acute phase of treatment. We monitored the course of psychotic-like symptoms following this course of therapy. RESULTS: 187 subjects endorsed at least one psychotic-like symptom, including not trusting close acquaintances (item 51), picking up hidden meanings (item 52), believing that others were talking about them (item 57), magical thinking (item 60) or unusual perceptual experiences (item 62). None of these patients met criteria for delusional depression as defined by the SCID. Overall response rates were 36.4% for patients who endorsed psychotic-like symptoms, and 53.3% for those who did not endorse psychotic-like symptoms (chi-squared = 11.1, P=0.001). The decrease in psychotic-like symptoms during the course of fluoxetine monotherapy was significant (P<0.05) in both responders and non-responders to treatment. CONCLUSION: A significant percentage of patients with non-psychotic major depression endorse subtle psychotic-like symptoms, many of which abate during monotherapy with fluoxetine regardless of response of the depressive symptoms.

The impact of galantamine on cognition and mood during electroconvulsive therapy: a pilot study.

OBJECTIVES: The purpose of this study was to: (1) assess the effectiveness of galantamine in the prevention of cognitive impairments during ECT treatment and (2) to explore the safety and tolerability of galantamine during ECT treatment. METHODS: Nine consecutive ECT patients were given galantamine 4 mg bid throughout the course of their ECT treatments followed by a second cohort of eight consecutive ECT patients who did not receive galantamine. Objective measures of cognitive functioning and depression severity were performed pre-ECT and post-ECT. Subjective ratings of depression, confusion, and side effects were obtained weekly. RESULTS: The two groups were similar in age, gender and admission Global Assessment Functioning (GAF) scores. There were no significant between group differences found with regards to mean seizure duration, energy administered to induce seizures, blood pressure, or heart rate during and post-ECT treatment. None of the patients discontinued galantamine due to side effects and there were no severe adverse drug reactions. Patients receiving galantamine performed significantly better on delayed memory and abstract reasoning following ECT. The galantamine group showed a greater but non-significant mood improvement (repeated measure ANOVA). CONCLUSIONS: Our data support the hypothesis that galantamine may reduce cognitive impairment during ECT, especially with regards to new learning. In addition, galantamine may also enhance the antidepressant action of ECT. Galantamine was both safe and well tolerated during ECT.

Testing the Efficacy of Attention Bias Modification for Suicidal Thoughts: Findings From Two Experiments.

This study explores whether four sessions of attention bias modification (ABM) decreases suicide-specific attentional bias. We conducted two experiments where suicide ideators completed either a Training or Control version of ABM, a computer-based intervention intended to target attentional bias. Suicide-specific attentional bias was measured using adapted Stroop and probe discrimination tasks. The first experiment with community-based suicide ideators did not show that ABM impacts attentional bias or suicidal ideation. The second experiment with clinically severe suicidal inpatients yielded similar results. Post-hoc findings suggest that the type of attentional bias targeted by the current intervention may differ from the type that marks suicide risk. There remains little to no evidence that the ABM intervention changes suicide-specific attentional bias or suicidal ideation.

Envisaging the adoption process to strengthen gay- and lesbian-headed families: recommendations for adoption professionals.

Although a growing number of child placement agencies are serving lesbians and gay men, a dearth of literature exists for adoption agency policies and practices related to working with this population. This article explores the unique characteristics and strengths of prospective gay and lesbian adoptive parents throughout each of the three phases of the adoption process-preplacement, placement, and postplacement-as well as provides suggestions for adoption professionals working with gays and lesbians. Data from a recent qualitative study of single, gay adoptive fathers are used to illustrate examples and expose areas of potential strengths of adoptive parents not generally explored in the preplacement or preparatory stage. Special attention also is given to the continuing needs of adoptive families headed by gays and lesbians after adoptive placement. Specifically explored are the needs for developing linkages with similar families, as well as providing resources designed to promote successful outcomes of adopted children raised by gays and lesbians.

An open study of olanzapine and fluoxetine for psychotic major depressive disorder: interim analyses.

BACKGROUND: Although atypical antipsychotic agents are commonly used in the treatment of psychotic depression, there are no published prospective studies on their use in this condition. The aim of this study was to assess, by interim analyses, the efficacy of the atypical antipsychotic agent olanzapine in combination with the selective serotonin reuptake inhibitor antidepressant agent fluoxetine. METHOD: We enrolled 27 patients (17 women [63.0%] and 10 men [37.0%]; mean +/- SD age: 41.2 +/- 14.7 years) with DSM-IV-defined major depressive disorder with psychotic features into an open trial of olanzapine, 5 to 20 mg/day, plus fluoxetine, 20 to 80 mg/day. Patients were assessed at each visit with the 17-item Hamilton Rating Scale for Depression and both the psychotic and mood modules of the Structured Clinical Interview for DSM-IV Axis I Disorders, Patient Edition. We are reporting the results of the first 6 weeks of treatment. RESULTS: Twenty-two (81.5%) of the 27 enrolled patients completed the 6-week open trial, and 5 (18.5%) dropped out, with only 2 (7.4%) dropping out due to side effects. Of the 27 patients, 74.1% (N = 20) met criteria for melancholic features, 14.8% (N = 4) had delusions alone, 18.5% (N = 5) had hallucinations alone, and 66.7% (N = 18) reported both delusions and hallucinations. In addition, the overall rates of response for the intent-to-treat group were as follows: depression response rate, 66.7% (N = 18); psychosis response rate, 59.3% (N = 16); psychotic depression response rate, 55.6% (N = 15); and psychotic depression remission rate, 40.7% (N = 11). CONCLUSION: The combination of olanzapine and fluoxetine appears to be a promising, safe, and effective treatment for psychotic depression. Double-blind studies are needed to confirm this impression.

Early drop-outs, late drop-outs and completers: differences in the continuation phase of a clinical trial.

OBJECTIVE: The purpose of this study was to assess the differences between early and late drop-outs and completers in the continuation phase of a clinical trial. METHODS: The authors studied 119 outpatients who were treatment responders in an 8-week open trial with fluoxetine 20 mg/day, and who were then enrolled in a 26-week clinical trial comparing the efficacy of fluoxetine versus fluoxetine and cognitive behavior therapy (CBT). Patients were assessed using the Structured Clinical Interview for DSM-III-R--Axis I (SCID-Patient Edition), Hamilton Depression Rating Scale (HAMD-17) and the following self-rated scales: Beck Depression Inventory (BDI), Beck Hopelessness Scale (BHS), Anxiety Sensitivity Index (ASI) and the Symptom Questionnaire (SQ) prior to starting the 26-week continuation phase. We defined "early drop-outs" (EDs) as patients who dropped out either at or prior to Visit 2 (which was at 2 months into the 6-month continuation phase); those dropping out at Visit 3 or later were defined as "late drop-outs" (LDs) (ED < or = 2 months; LD >2 months). The Kruskal-Wallis and the Mann-Whitney U tests were used for data analysis. RESULTS: Of the 119 patients, 83 were completers (mean age: 42.1+/-9.0 years; 46 [55%] women; age of onset of major depressive disorder [MDD] = 24.3+/-12.5 years), II were EDs (mean age: 38.1 + 13.0 years: 4 [36%] women; age of onset of MDD = 22.0+/-11.1 years) and 25 were LDs (mean age: 35.2+/-10.4 years; 12 [48%] women; age of onset of MDD = 24.6+/-11.6 years). LDs were significantly younger than completers (P<.01). There was no significant difference in age between EDs and LDs, nor between EDs and completers. EDs were more likely to have been depressed for a longer period of time compared to LDs (P< .05). EDs completers were depressed for a longer period of time compared to LDs (P< .05). CONCLUSIONS: Our data suggest that late drop-outs are significantly younger than completers, although age is not a predictor between early drop-outs and late drop-outs. Further, early drop-outs are depressed for a longer duration compared to late drop-outs completers are depressed for a longer duration than late dropouts, and Early drop-outs have significantly more social impairment compared to completers. Our study identified some patient characteristics significantly associated with dropping out of a long-term clinical trial.

Early drop-outs, late drop-outs and completers: differences in the continuation phase of a clinical trial.

OBJECTIVE: The purpose of this study was to assess the differences between early (EDs), late drop-outs (LDs) and completers in the continuation phase of a clinical trial. METHODS: The authors studied 119 outpatients who were treatment responders in an 8-week open trial with fluoxetine 20 mg/day, and who were then enrolled in a 26-week clinical trial comparing the efficacy of fluoxetine versus fluoxetine and cognitive behavior therapy (CBT). Patients were assessed using the Structured Clinical Interview for DSM-III-R-Axis I (SCID-Patient Edition), Hamilton Depression Rating Scale (HAMD-17) and the following self-rated scales: Beck Depression Inventory (BDI), Beck Hopelessness Scale (BHS), Anxiety Sensitivity Index (ASI) and the Symptom Questionnaire (SQ) prior to starting the 26-week continuation phase. We defined 'EDs' as patients who dropped out either at or prior to Visit 2 (which was at 2 months into the 6-month continuation phase); those dropping out at Visit 3 or later were defined as 'LDs' (ED < or = 2 months and LD > 2 months). The Kruskal-Wallis and the Mann-Whitney U tests were used for data analysis. RESULTS: Of the 119 outpatients, 83 were completers (mean age: 42.1 +/- 9.0 years, 46 [55%] women, age of onset of major depressive disorder [MDD] = 24.3 +/- 12.5 years), 11 were EDs (mean age: 38.1 +/- 13.0 years, 4 [36%] women, age of onset of MDD = 22.0 +/- 11.1 years) and 25 were LDs (mean age: 35.2 +/- 10.4 years, 12 [48%] women, age of onset of MDD = 24.6 +/- 11.6 years). LDs were significantly younger than completers (P<.01). There was no significant difference in age between EDs and LDs, nor between EDs and completers. EDs and completers were depressed for a longer period of time compared to LDs (P<.05). EDs also had significantly greater overall impairment in social adjustment compared to completers (P<.05). CONCLUSIONS: Our data suggest that LDs are significantly younger than completers, although age is not a predictor between EDs and LDs. Further, EDs and completers are depressed for a longer duration than LDs, and EDs have significantly greater social impairment compared to completers. Our study identified some patient characteristics significantly associated with dropping out of a long-term clinical trial.

Effects of adding cognitive therapy to fluoxetine dose increase on risk of relapse and residual depressive symptoms in continuation treatment of major depressive disorder.

Patients with major depressive disorder remain at risk for relapse following remission and often continue to experience subthreshold symptoms. This study compared the rate of relapse of major depressive disorder and the prevalence of residual depressive symptoms during the continuation phase for patients treated with fluoxetine dose increase alone or in combination with cognitive therapy. A total of 132 outpatients with major depressive disorder who achieved remission with 8 weeks of treatment with fluoxetine 20 mg had the dose increased to 40 mg. They were randomized to receive cognitive therapy or medication management alone and were followed for up to 28 weeks for depressive relapse and change in depressive symptoms. A total of 47 (35.6%) out of 132 patients did not complete the 28-week continuation phase. Rates of discontinuation or relapse did not differ significantly between the groups. Change in residual symptoms or wellbeing as measured by Hamilton Depression Scale score or Symptom Questionnaire self-report also did not differ between groups. In this sample of outpatients in continuation phase treatment for major depressive disorder, the combination of cognitive therapy and fluoxetine 40 mg failed to yield any significant benefit in symptoms or relapse rates over fluoxetine 40 mg alone during 28 weeks of follow-up.