Modafinil and armodafinil treatment for fatigue for HIV-positive patients with and without chronic hepatitis C.

Fatigue is prevalent among patients with hepatitis C virus (HCV) and with HIV/AIDS but there are no established fatigue treatments for either condition or their combination. We analysed data from three trials of modafinil or armodafinil for HIV-positive patients with fatigue, including 36 co-infected with HCV, to compare treatment response and safety parameters related to HCV status. One hundred and twenty patients received active drug and 70 were randomized to placebo. Fatigue response rate to modafinil/armodafinil was 100% for patients with HCV (18/18) and 73% (74/102) for patients without HCV. Placebo response rate was 28% (5/18) and 29% (15/52), respectively. Depressive symptoms improved only when energy improved. Viral load declined from baseline after 12 and 26 weeks of active medication. CD4 cell count did not change, nor did alanine transaminase and aspartate aminotransferase for patients with HCV. Patients with haematocrit below the reference range responded, as well as patients whose values were within the reference range. Modafinil and armodafinil appear effective and well tolerated for treating fatigue among both HCV-positive and HCV-negative patients with HIV/AIDS, suggesting that they may hold promise for HIV-positive patients considering alpha interferon/ribavirin treatment for HCV. Further investigation in a focused trial is warranted.

Prevalence of fatigue and depression in ALS patients and change over time.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) patients report both fatigue and depression. It is not clear how frequently each occurs, to what extent they occur together, how each relates to ALS disease status, or their stability over time. OBJECTIVE: To assess frequency and persistence of fatigue and depression, and relationship to ALS disease status, for patients attending an ALS interdisciplinary centre for routine 3-month visits. METHOD: Measures included the Fatigue Severity Scale, Patient Health Questionnaire-9. ALS Functional Rating Scale -- Revised and forced vital capacity, rate of disease progression, and bulbar/nonbulbar disease onset. RESULTS: 223 patients completed the ratings once; of these, 113 completed them twice, and 65 on three visits. At baseline, 44% (99/223) had clinically significant fatigue, including 34 patients who also had a depressive disorder; 7% (16/223) had major or minor depression only, and 48% (108/223) had neither condition. Fatigue was associated with greater ALS severity, but depression was not. Among the 113 patients seen 3 months later, 75% (33/44) who were fatigued at Time 1 remained fatigued, while 48% (10/21) remained depressed. New-onset fatigue was reported by 22% (25/113), and new-onset depression by 6% (7/113). For the 65 patients seen a third time, rates remained nearly the same. CONCLUSION: Fatigue was more prevalent and persistent than depression, although 15% (34/223) of patients had both conditions. Fatigue but not depression was associated with ALS severity. The two conditions appear to be independent, although sometimes co-occurring, and both warrant consideration in evaluating patient functioning and treatment.

Anxiety syndromes and symptoms among men with AIDS: a longitudinal controlled study.

This 2-year longitudinal study assessed prevalence of Axis I anxiety disorders and anxiety symptoms and their relationship to manifestations of HIV illness in a sample of nonintravenous drug users. The sample included 173 homosexual men with HIV or AIDS (HIV+/AIDS) and 84 homosexual men negative for HIV or AIDS (HIV-). Data were compared with national prevalence rates to provide a framework for interpretation. No significant differences were observed. However, compared with the general population, both HIV+/AIDS and HIV- men reported more anxiety symptoms and stress. For the HIV+/AIDS group there was a positive relationship between anxiety and HIV symptoms, fatigue, and physical limitations. No changes in rates or levels of anxiety were observed in those whose immunologic markers improved or worsened over the 2 years.

The relationship between employment and neuropsychological impairment in HIV infection.

The relationship between neurocognitive impairment and employment in a cohort of 130 predominantly symptomatic individuals with HIV-1 infection was examined. Participants were classified as employed (full or part-time for pay) or unemployed (N = 64) and administered a neuropsychological test battery. When covarying for CD4 count, age, and physical limitations, the results revealed that unemployed men performed below that of employed participants on tasks of memory, set shifting-cognitive flexibility, and psychomotor speed. The results are discussed within the context of similar findings in other illnesses.

Subjective memory complaints prior to and following electroconvulsive therapy.

Using the Squire Subjective Memory Questionnaire (SSMQ), depressed patients rated their memory functioning prior to a course of brief pulse, electroconvulsive therapy (ECT) within the 1 week following the course and 2 months later. Normal controls made similar ratings at comparable intervals. Prior to ECT, patients reported poorer memory functioning than controls. There was marked improvements in the patients' self-reports shortly following ECT, and at 2-month follow-up SSMQ scores were generally comparable in patients and controls. At all time points, the severity of depressive symptoms was strongly associated with patients' reports of memory dysfunction. SSMQ subscales ("depression" and "ECT" items) were not differentially sensitive to effects of ECT or depression. Relations between ECT treatment parameters and changes in patients' self-evaluations only emerged after controlling for clinical state change. Shortly following ECT, there were no relations between SSMQ scores and objective measures of cognitive functioning. However, 2 months following ECT, there was a suggestion that greater retrograde amnesia for autobiographical memories was associated with self-rating of greater memory impairment.

Predictors of retrograde amnesia following ECT.

OBJECTIVE: Substantial progress has been made in identifying how the treatment parameters used in ECT impact on cognitive side effects. However, there is limited information regarding individual differences in vulnerability to these side effects. The authors examined patients' pretreatment global cognitive status and postictal orientation recovery time as potential predictors of the magnitude of retrograde amnesia for autobiographical memories after ECT. METHOD: Seventy-one inpatients with major depressive disorder were randomly assigned to four ECT conditions that varied in electrode placement (right unilateral versus bilateral) and stimulus dosage (low versus high intensity). Orientation recovery time was assessed at virtually every session during the course of ECT. Global cognitive status was assessed with the modified Mini-Mental State examination before treatment, during the week after termination of treatment, and 2 months after treatment ended. Retrograde amnesia was assessed at these same time points with the Autobiographical Memory Interview. RESULTS: Pre-ECT global cognitive status and the duration of postictal disorientation were strong predictors of the magnitude of retrograde amnesia in the week after the course of ECT and at 2-month follow-up. In general, these relationships were maintained regardless of technical parameters in the administration of the ECT. CONCLUSIONS: Patients who manifest global cognitive impairment before treatment and patients who experience prolonged disorientation in the acute postictal period may be the most vulnerable to persistent retrograde amnesia for autobiographical information.

Hearing loss and asymmetry in major depression.

To assess patterns of hearing loss and asymmetry in major depressive disorder (MDD), pure-tone and brief-click audiometric thresholds were measured in 59 inpatients with MDD and 40 normal control subjects. For both tasks, patients had higher bilateral thresholds, with marked hearing loss for the highest pure-tone frequency. At lower frequencies, patients displayed significant asymmetry, with poorer hearing in the left ear. After ECT, patients maintained the bilateral hearing losses; however, the baseline asymmetry resolved. These findings suggest that bilateral hearing loss may be a stable characteristic in severe depression. Poorer left ear pure-tone hearing may be present during the depressed state. The baseline asymmetry in audiometric deficits suggests right-hemisphere dysfunction in severe MDD.

Effects of stimulus intensity and electrode placement on the efficacy and cognitive effects of electroconvulsive therapy.

BACKGROUND: The efficacy of electroconvulsive therapy in major depression is established, but the importance of the electrical dosage and electrode placement in relation to efficacy and side effects is uncertain. METHODS: In a double-blind study, we randomly assigned 96 depressed patients to receive right unilateral or bilateral electroconvulsive therapy at either a low electrical dose (just above the seizure threshold) or a high dose (2.5 times the threshold). Symptoms of depression and cognitive functioning were assessed before, during, immediately after, and two months after therapy. Patients who responded to treatment were followed for one year to assess the rate of relapse. RESULTS: The response rate for low-dose unilateral electroconvulsive therapy was 17 percent, as compared with 43 percent for high-dose unilateral therapy (P = 0.054), 65 percent for low-dose bilateral therapy (P = 0.001), and 63 percent for high-dose bilateral therapy (P = 0.001). Regardless of electrode placement, high dosage resulted in more rapid improvement (P < 0.05). Compared with the low-dose unilateral group, the high-dose unilateral group took 83 percent longer (P < 0.001) to recover orientation after seizure induction, whereas the combined bilateral groups took 252 percent longer (P < 0.001). During the week after treatment, there was three times more retrograde amnesia about personal information with bilateral therapy (P < 0.001). There were no differences between treatment groups in cognitive effects two months after treatment. Forty-one of the 70 patients who responded to therapy (59 percent) relapsed, and there were no differences between treatment groups. CONCLUSIONS: Increasing the electrical dosage increases the efficacy of right unilateral electroconvulsive therapy, although not to the level of bilateral therapy. High electrical dosage is associated with a more rapid response, and unilateral treatment is associated with less severe cognitive side effects after treatment.