123I‐metaiodobenzylguanidine scintigraphy in Parkinson's disease and related disorders

Autonomic dysfunction is common in Lewy body disorders (Parkinson's disease, Dementia with Lewy Bodies, Pure Autonomic Failure, and REM sleep disorder). The loss of post‐ganglionic myocardial sympathetic nerve fibers is a prominent feature of autonomic dysfunction in such disorders. ¹²³I‐metaiodobenzylguanidine (MIBG) scintigraphy that visualizes catecholaminergic terminals in vivo is a biomarker used to detect cardiac sympathetic degeneration. Abnormal MIBG uptake has been consistently reported in Lewy body disorders. Some studies agree in the notion that increasing bradykinesia is related with an incremental cardiac sympathetic denervation, whereas tremor is not closely linked to cardiac denervation. “Atypical” parkinsonian syndromes, including Multiple System Atrophy, Progressive Supranuclear Palsy, and others, show modest reductions of cardial MIBG uptake. MIBG scintigraphy is moderately sensitive and specific in differentiating Parkinson's disease from such syndromes. Conversely, its sensitivity and specificity might be better in cognitively impaired patients, helping differential diagnosis between Dementia with Lewy Bodies, and Alzheimer disease. Confounding factors (comorbidities, comedications) should be carefully controlled before analyzing MIBG scintigraphy. © 2009 Movement Disorder Society     

Escitalopram in the treatment of major depressive disorder in primary‐care settings: an open‐label trial

Background: The present trial was designed to assess the efficacy and safety of escitalopram prescribed to patients seeking treatment of major depressive disorder (MDD) in a Canadian primary‐care setting. Methods: Investigators (mainly primary‐care physicians) enrolled patients with MDD from their daily practice. Patients were treated with escitalopram (flexible dose 10–20 mg/day) for up to 24 weeks. Efficacy assessments included the Montgomery–Åsberg Depression Rating Scale (MADRS), the Clinical Global Impression‐Improvement and ‐Severity scales (CGI‐I, CGI‐S), the Patient Global Evaluation (PGE), and the Medical Outcome Study 36‐item Short Form (SF‐36). Results: Out of the 647 patients enrolled, 461 (71%) completed 24 weeks of treatment. The most common reason for discontinuation was adverse events (10%). The mean MADRS score decreased from 30.7 at baseline to 10.9 at the end of 24 weeks (last observation carried forward, LOCF). Remission (MADRS≤12) was achieved by 65.5% of patients (LOCF). Symptom improvements were confirmed by global ratings of improvement made by physicians (CGI‐I) as well as patients PGE. There was improvement on all dimensions of the SF‐36, suggesting an overall improvement in quality of life. Conclusions: Escitalopram was well tolerated, safe, and efficacious. Escitalopram can be used with confidence to treat patients with MDD in Canadian primary‐care settings. Depression and Anxiety, 2008. © 2008 Wiley‐Liss, Inc.     

The brain-derived neurotrophic factor (BDNF) polymorphism Val66Met is associated with neither serum BDNF level nor response to selective serotonin reuptake inhibitors in depressed Japanese patients

Background

We investigated the relationship between a brain-derived neurotrophic factor (BDNF) polymorphism (Val66Met) and the clinical response of patients with major depressive disorder to selective serotonin reuptake inhibitors (SSRIs; here, paroxetine and sertraline). In addition, serum BDNF levels in these patients were considered together with the clinical response.

Methods

A total of 132 patients who met the DSM-IV criteria for major depressive disorder were enrolled in the study. 54 of these patients were male and 78 were female (age range, 20-74 years; mean ± S.D., 51 ± 15). The patients' clinical improvement was evaluated using the 17-item Hamilton Rating Scale for Depression (HAMD-17) before (T0) and at 8 weeks after the administration of SSRI treatment (T8). Patients with at least a 50% decrease in the HAMD-17 score were classified as responders.

Results

No correlation was observed between the BDNF Val66Met polymorphism and response to SSRIs or between the BDNF Val66Met polymorphism and serum BDNF levels at T0. An inverse correlation was found between serum BDNF levels and HAMD-17 scores at T0.

Conclusions

These results suggest that the BDNF Val66Met polymorphism is independent of both the response to SSRI treatment and serum BDNF levels. The findings in the present study reconfirm that the serum BDNF level is a state biomarker for depression.     

Early diagnosis of Lewy body disease in patients with late‐onset psychiatric disorders using clinical history of rapid eye movement sleep behavior disorder and [123I]‐metaiodobenzylguanidine cardiac scintigraphy

Aim

Rapid eye movement sleep behavior disorder (RBD) and psychiatric symptoms often antedate the clinical diagnosis of Parkinson's disease or dementia with Lewy bodies. The purpose of this study was to investigate RBD and its relevance to Lewy body disease (LBD) in patients with late‐onset psychiatric disorders.

Methods

Study subjects included 19 patients with late‐onset psychiatric disorders who exhibited REM sleep without atonia (RWA), which is a hallmark of RBD on polysomnography, at our psychiatric ward. Clinical profiles and radiological findings by cardiac [¹²³I]‐metaiodobenzylguanidine ([¹²³I]‐MIBG) scintigraphy and imaging for the dopamine transporter (DAT) were compared between patients with and without RBD symptoms. The correlations between the percentage of RWA in the total rapid eye movement sleep (%RWA) and radiological findings were also investigated.

Results

Nine patients reported RBD symptoms only on specific questioning, but clinical profiles, including the prevalence of antipsychotropic usage, did not differ when compared to the remaining 10 patients without RBD (incidental RWA group). The median %RWA was significantly higher in the definite RBD group than in the incidental RWA group. Although the cardiac [¹²³I]‐MIBG uptake was significantly lower in the definite RBD group than in the incidental RWA group, there was overlap in the specific binding ratio on DAT scan.

Conclusion

The severity of %RWA was highly correlated with the value of cardiac [¹²³I]‐MIBG uptake, but not with specific binding ratio on DAT scan. Clinical history of RBD and cardiac [¹²³I]‐MIBG scintigraphy are helpful for an early differential diagnosis of LBD from late‐onset psychiatric disorders, even before parkinsonism or dementia appears.

     

Prospective evaluation of the serotonin syndrome in depressed inpatients treated with clomipramine

The serotonin syndrome, induced by serotoninergic agents, includes confusion, agitation, myoclonus, diaphoresis, tremor and diarrhea. The authors prospectively evaluated all these symptoms in 38 depressed inpatients fullfilling DSM-III-R criteria for major depression. Sixteen (42%) of 38 patients presented at least one symptom of serotonin syndrome. In 14 cases tremor and myoclonus occurred simultaneously, and 10 patients presented at the same time tremor plus myoclonus, diaphoresis and shivering. Except for 2 patients, symptoms were transient, lasted less than 1 week and disappeared with the pursuit of treatment.     

Measurement of 5-HT1A receptor binding in depressed adults before and after antidepressant drug treatment using positron emission tomography and [11C]WAY-100635

OBJECTIVE: To assess effects of chronic antidepressant drug treatment on serotonin type-1A receptor (5-HT(1A)R) binding potential (BP) in major depressive disorder. METHODS: Depressed subjects (n = 27) were imaged using PET and [(11)C]WAY-100635 at baseline and following a median of 9.4 weeks of treatment with selective serotonin reuptake inhibitor or dual reuptake inhibitor antidepressant agents. Fifteen subjects had complete pre- and post-treatment scan data. The 5-HT(1A)R BP was derived from the tissue time-radioactivity concentrations from regions-of-interest defined a priori, using a simplified reference tissue model (SRTM), and in a subset of subjects, compartmental modeling (CMOD). RESULTS: Chronic treatment had no effect on pre- or post-synaptic 5-HT(1A)R BP, as confirmed by both the SRTM and CMOD analyses. These results were unaffected by treatment response status and were consistent across brain regions. Among the 22 subjects for whom the clinical response-to-treatment was established, the treatment nonresponders (n = 7) had higher baseline BP values in the left (P = 0.01) and right orbital cortex (P = 0.02) than the responders (n = 15). CONCLUSIONS: Chronic antidepressant drug treatment did not significantly change cerebral 5-HT(1A)R binding, consistent with preclinical evidence that the alterations in serotonergic function associated with antidepressant drug administration are not accompanied by changes in 5-HT(1A)R density. Higher baseline 5-HT(1A)R binding was associated with poorer response to treatment.     

Meta‐analysis of 123I‐MIBG cardiac scintigraphy for the diagnosis of Lewy body–related disorders

Patients with parkinsonism pose a diagnostic challenge. Parkinson's disease may be difficult to distinguish from multiple system atrophy and progressive supranuclear palsy, whereas Parkinson's disease and dementia with Lewy bodies can be difficult to distinguish from Alzheimer's disease and other dementias. A number of studies have found diminished cardiac ¹²³I‐metaiodobenzylguanidine uptake in Lewy body–related conditions (Parkinson's disease and Lewy body dementia). In 2005, the Dementia With Lewy Bodies Consortium considered ¹²³I‐metaiodobenzylguanidine cardiac scintigraphy a “supportive” diagnostic feature, based on limited evidence. We report a meta‐analysis of the literature and an assessment of the utility of ¹²³I‐metaiodobenzylguanidine for the diagnosis of dementia with Lewy bodies and Parkinson's disease. A search was conducted of articles published between 1950 and June 2010. Forty‐six studies involving neuropsychiatric and movement disorders, comprising 2680 subjects, were included in the analysis. A mixed‐effects regression model was used to analyze the delayed mean heart‐to‐mediastinum ratio of ¹²³I‐metaiodobenzylguanidine uptake. ¹²³I‐metaiodobenzylguanidine cardiac scintigraphy sensitively detected and specifically distinguished 2 diagnostic clusters: (1) Parkinson's disease, dementia with Lewy bodies, and rapid eye movement sleep behavior disorder; and (2) normal controls and patients with Alzheimer's disease, multiple system atrophy, progressive supranuclear palsy, vascular dementia, and frontotemporal dementia. The area under the receiver operating characteristic curve was 0.987 at a cluster discriminatory heart‐to‐mediastinum ratio threshold of 1.77. This threshold yielded 94% sensitivity and 91% specificity for the discrimination of these diagnostic clusters. ¹²³I‐metaiodobenzylguanidine cardiac scintigraphy can accurately distinguish between 2 movement disorders, Parkinson's disease and multiple system atrophy, and between 2 common causes of dementia, Alzheimer's disease and dementia with Lewy bodies. © 2011 Movement Disorder Society     

Therapeutic drug monitoring of selective serotonin reuptake inhibitors influences clinical dosing strategies and reduces drug costs in depressed elderly patients

OBJECTIVE: This study was initiated in order to describe and evaluate the effects of a therapeutic drug monitoring (TDM) routine of selective serotonin reuptake inhibitors (SSRIs) on treatment strategies and drug costs in depressed elderly patients. METHOD: Blood samples were drawn from elderly depressed patients and analysed for steady-state trough serum concentrations of citalopram (n = 48), paroxetine (n = 48) or sertraline (n = 39). A global efficacy evaluation was made at baseline and after 6-9 months. Antidepressant drug costs before and after TDM were estimated. RESULTS: Eight samples were excluded due to technical problems or noncompliance. In 65 of the 127 (51.2%) remaining cases, the treatment strategy was changed according to the TDM outcome, in most a reduction of the prescribed dose. Bioanalytical TDM costs included the antidepressant drug costs after TDM were reduced by 10.2%. CONCLUSION: The results support the utility of TDM in the search for the individual minimum effective SSRI dose in the elderly.     

Naturalistic study of the early psychiatric use of citalopram in the United States

We obtained information on the efficacy and safety of citalopram in settings that resemble actual clinical practice. A total of 1,783 patients participated in this open, uncontrolled, naturalistic Phase IV evaluation of citalopram at 447 U.S. investigative sites. Participants were selected by guidelines in the citalopram package insert using minimal exclusion criteria. Citalopram dosing began at 20 mg/day and could be titrated to 60 mg/day. Outcomes included the Clinical Global Impressions-Improvement scale (CGI-I) and a Patient Global Evaluation. Separate analyses were performed on patients with a primary diagnosis of major depressive disorder (MDD) (76%) who reported intolerance or nonresponse to previous selective serotonin reuptake inhibitors (SSRIs). Patients included tended to have treatment-resistant or intolerant, chronic or recurrent, comorbid depression with a mean duration of illness of 10 years. At study completion, more than 68% of treatment completers were classified as responders (CGI-I score of 1 or 2). Endpoint analyses showed response rates of 54% in all patients, 56% in patients with MDD, 49% in SSRI nonresponsive patients, and 53% in patients with a history of SSRI intolerance. Nausea (9.8%) and headache (7.3%) were the most often reported adverse events. Patients with a history of SSRI intolerance had a discontinuation rate of 21.8%, whereas those without such a history had a discontinuation rate of 13.3%. Citalopram administered at an average dose of 23.6 mg/day was associated with favorable outcomes and was generally well tolerated.