Prasad R. Padala

Risperidone monotherapy for post-traumatic stress disorder related to sexual assault and domestic abuse in women

Post-traumatic stress disorder is a common, chronic, and often disabling mental illness. Selective serotonin reuptake inhibitors are the usual first-line treatment for post-traumatic stress disorder, but many patients fail to respond adequately. Thus, other treatment options, including the atypical antipsychotics such as risperidone, need to be tested. Women between the ages of 19 and 64 years with post-traumatic stress disorder were enrolled. Symptom severity was rated at baseline using the Treatment Outcomes Post-traumatic Stress Disorder Scale-8, Hamilton Rating Scale for Anxiety, Hamilton Rating Scale for Depression, and Clinician Administered Post-traumatic Stress Disorder Scale. After washout from other psychotropic medications, 20 participants were randomized to either risperidone or placebo. Total score on the Treatment Outcomes Post-traumatic Stress Disorder Scale-8 served as the primary outcome measure. Repeated-measures analysis of variance was followed by Newman–Keuls tests. A significant main effect exists for visits using the Treatment Outcomes Post-traumatic Stress Disorder Scale-8 raw score. For the treatment group, the difference between baseline Treatment Outcomes Post-traumatic Stress Disorder Scale-8 scores and treatment visit scores was significant beginning at visit 6 and continued through visit 11. No significant difference observed between baseline and any treatment visit for the placebo group. The Clinician Administered Post-traumatic Stress Disorder Scale, Hamilton Rating Scale for Anxiety, and Hamilton Rating Scale for Depression data revealed a similar pattern. In this small pilot study, risperidone monotherapy was more effective than placebo in the treatment of post-traumatic stress disorder.

Wii-Fit for Improving Gait and Balance in an Assisted Living Facility: A Pilot Study

Objectives. To determine the effects on balance and gait of a Wii-Fit program compared to a walking program in subjects with mild Alzheimers dementia (AD). Methods. A prospective randomized (1 : 1) pilot study with two intervention arms was conducted in an assisted living facility with twenty-two mild AD subjects. In both groups the intervention occurred under supervision for 30 minutes daily, five times a week for eight weeks. Repeated measures ANOVA and paired t-tests were used to analyze changes. Results. Both groups showed improvement in Berg Balance Scale (BBS), Tinetti Test (TT) and Timed Up and Go (TUG) over 8 weeks. However, there was no statistically significant difference between the groups over time. Intragroup analysis in the Wii-Fit group showed significant improvement on BBS (P = 0.003), and TT (P = 0.013). The walking group showed a trend towards improvement on BBS (P = 0.06) and TUG (P = 0.07) and significant improvement in TT (P = 0.06). Conclusion. This pilot study demonstrates the safety and efficacy of Wii-Fit in an assisted living facility in subjects with mild AD. Use of Wii-Fit resulted in significant improvements in balance and gait comparable to those in the robust monitored walking program. These results need to be confirmed in a larger, methodologically sound study.

Methylphenidate for Apathy and Functional Status in Dementia of the Alzheimer Type

OBJECTIVE Apathy is the most common behavioral problem in persons with dementia of the Alzheimer type (DAT). Treatment of apathy in DAT is not systematically studied. The purpose of this study was to evaluate the response of apathy to methylphenidate treatment and to examine whether functional status improved. METHODS The authors conducted a 12-week open-labeled study with immediate release formulation of methylphenidate. Twenty-three patients with DAT scoring >40 on the Apathy Evaluation Scale (AES) were recruited. Repeated measures analysis of variance and correlation analysis were performed. RESULTS None of the patients dropped out of the study because of adverse events. Significant improvement in apathy was noted during 12 weeks. Significant improvement was also noted in depression, Mini-Mental State Examination score, and functional status. There was no correlation between changes in the AES and depression scores. CONCLUSIONS Methylphenidate was well tolerated in these patients with DAT. Apathy improved with the use of methylphenidate.

The effect of HMG-CoA reductase inhibitors on cognition in patients with Alzheimer's dementia: a prospective withdrawal and rechallenge pilot study.

BACKGROUND Statins are well-known for their cardiovascular benefits. However, the cognitive effects of statins are not well understood. We hypothesized that individuals with preexisting dementia would be more vulnerable to statin-related cognitive effects. OBJECTIVE The aim of this study was to evaluate the impact on cognition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor (statin) discontinuation and rechallenge in individuals with Alzheimers dementia (AD) on statins at baseline. METHODS A 12-week prospective, open-label study was conducted in a geriatric clinic setting. Eighteen older subjects underwent a 6-week withdrawal phase of statins followed by a 6-week rechallenge. The primary outcome measure was cognition, measured by the Mini-Mental State Examination (MMSE); secondary outcome measures were the Consortium to Establish a Registry for Alzheimers Disease (CERAD) neuropsychological battery, Activities of Daily Living (ADL) scale, Instrumental ADL (IADL) scale, and fasting cholesterol. The change in outcome measures was assessed using repeated-measures ANOVA and paired t tests. RESULTS At the end of the intervention, there was a significant difference across time for MMSE score (P = 0.018), and total cholesterol (P = 0.0002) and a trend toward change across time for ADL (P = 0.07) and IADL (P = 0.06) scale scores. Further analyses using paired t tests indicated improvement in MMSE scores (Δ1.9 [3.0], P = 0.014) with discontinuation of statins and a decrease in MMSE scores (Δ1.9 [2.7], P = 0.007) after rechallenge. Total cholesterol increased with statin discontinuation (P = 0.0003) and decreased with rechallenge (P = 0.0007). The CERAD score did not show a change across time (P = 0.31). There was a trend toward improvement in ADL (P = 0.07) and IADL (P = 0.06) scale scores with discontinuation of statins, but no change with rechallenge. CONCLUSIONS This pilot study found an improvement in cognition with discontinuation of statins and worsening with rechallenge. Statins may adversely affect cognition in patients with dementia.

Simvastatin-Induced Decline in Cognition

Objective: To describe a case of new-onset cognitive difficulties in an older patient after initiation of simvastatin therapy. Case Summary: A 64-year-old man developed cognitive difficulties within one week after starting simvastatin 40 mg/day. There was a 3 point decline from baseline in the Mini-Mental State Exam (MMSE) score 2 weeks after simvastatin was initiated, as well as declines in the Activities of Daily Living and Instrumental Activities of Daily Living scales. Simvastatin was discontinued, and the patients cognition improved to baseline within 6 weeks. Rechallenge with simvastatin at half the original dose was attempted. His cognition deteriorated over a 2 week period. Simvastatin was stopped, and the patients MMSE scores returned to baseline within 4 weeks. Discussion: This patient developed new-onset problems with short-term memory, long-term memory, and item misplacement in addition to the baseline problems with names and word-finding that had been present prior to beginning statin therapy. Decreased cognition identified with neuropsychological tests has been shown in clinical trials with simvastatin; however, as of August 23, 2006, this is the first report of cognitive and functional problems that have been documented using standardized instruments. The Naranjo probability scale revealed a highly probable adverse reaction of cognitive decline associated with simvastatin therapy. Conclusions: Statins are commonly used in the older population. Simvastatin appeared to be associated with worsened cognition in our patient, an older person with preexisting memory problems. Statins should be used with caution in this vulnerable population.

Apathy associated with neurocognitive disorders: Recent progress and future directions

Apathy is common in neurocognitive disorders (NCDs) such as Alzheimers disease and mild cognitive impairment. Although the definition of apathy is inconsistent in the literature, apathy is primarily defined as a loss of motivation and decreased interest in daily activities.

Reversal of SSRI-Associated Apathy Syndrome by Discontinuation of Therapy

Objective: To report 6 cases of selective serotonin reuptake inhibitor (SSRI)– associated apathy syndrome. Case Summaries: In all 6 cases, the patient reported loss of motivation while being treated with an SSRI. Loss of motivation was of new onset and temporally associated with the use of the SSRI. A trial of discontinuation of the SSRI was performed in all 6 patients and 2 I were started on bupropion while cross-tapering from the SSRI. During the treatment trials, depression and apathy were monitored in all patients. Each case was assessed using the Apathy Evaluation Scale, Clinician version (AES-C), and by evaluating how the patient responded to discontinuation of the SSRI. Discussion: Scores on the AES-C improved significantly in all 6 cases after the SSRI was discontinued. Improvement was also seen in the motivation, novelty, and persistence subdomain scores of the AES-C. A pretreatment AES-C score was available only in the first case. Based on the Naranjo probability scale, there was a probable cause of apathy syndrome with SSRI therapy in the first case and a possible association in the rest of the cases. Conclusions: In some patients SSRIs may cause an apathy syndrome that can be reversed through discontinuation of the agent. When evaluating patients being treated with an SSRI, clinicians should have a high degree of suspicion and specifically inquire for this iatrogenic form of apathy syndrome.

Modafinil Therapy for Apathy in an Elderly Patient

Objective: To present a case of successful treatment of apathy syndrome with modafinil. Case Summary: A 78-year-old man with dementia and depression was also experiencing apathy that did not respond to antidepressants including escitalopram, a selective serotonin-reuptake inhibitor (SSRI). Escitalopram was discontinued and modafinil, a novel vigilance-promoting agent pharmacologically distinct from stimulants, was used to successfully treat the apathy. The dosage regimen was initiated at 50 mg and titrated to 200 mg/day over 4 weeks. Apathy was assessed using the Apathy Evaluation Scale developed specifically to identify apathy and also to differentiate this from depression. Discussion: Apathy, a common behavioral problem, is often mistaken for depression; however, apathy differs from depression in symptomatology, clinical presentation, and treatment options. SSRIs, a common treatment for depression, are known to cause or increase apathy. Deficits in the dopamine receptor system are involved in the etiology of apathy; modafinils increased dopaminergic transmission is thought to help alleviate apathy. Due to its relative lack of drug interactions, modafinil is a good alternative for elderly patients, who often receive multiple medications. Apathy improved significantly after treatment with modafinil in this patient. To the best of our knowledge, as of January 22, 2007, this is the first report of modafinil treatment of apathy syndrome. Conclusions: Modafinil may be useful in treating apathy syndrome. Its role in the treatment of apathy requires further testing in clinical trials.

Methylphenidate May Treat Apathy Independent of Depression

OBJECTIVE To report a case of apathy treated with methylphenidate in which improvement in apathy was independent of improvement of depression. CASE SUMMARY A 47-year-old woman with a 20-year history of recurrent major depression was diagnosed as having significant apathy with lack of initiative and motivation. Over the course of a 4-week treatment regimen with methylphenidate, her apathy, as measured by the Apathy Evaluation Scale, improved, with her score decreasing from 57 to 31. During this period, her depression, as assessed by the 21-item Hamilton Rating Scale for Depression, remained unchanged. DISCUSSION Our report of improvement of apathy with methylphenidate is consistent with other reports in the literature, although previous studies have not specifically used the rating scales to assess apathy. Even though this patient had experienced apathy for a long time, it had not been detected due to lack of direct questioning. In this case, as noted, the improvement of apathy was independent of improvement in depression. CONCLUSIONS A high degree of suspicion and specific inquiry is required for identification of apathy. Once detected, methylphenidate may be beneficial in its treatment, a strategy that may work independently of augmentation of antidepressants.

Prospective study of posttraumatic stress disorder and disease activity outcomes in US veterans with rheumatoid arthritis

To examine the relationship between posttraumatic stress disorder (PTSD) and disease activity in US veterans with rheumatoid arthritis (RA).