Armando Piccinni

Psychiatric comorbidity in a population of Parkinson's disease patients

Behavioural disturbances are frequently observed in Parkinsons disease (PD), including mood and anxiety disorders. The existence of a comorbidity between such psychiatric disorders in PD patients has been suggested only in a few studies. To assess the prevalence of mood and anxiety disturbances, and the rate of comorbidity of such disorders in PD. Secondary aim was to correlate the prevalence of psychiatric disorders in PD with age, sex, laterality of motor symptomatology, clinical features, severity of disease, age of onset and PD duration, and anti‐parkinsonian therapy. Ninety consecutive PD outpatients, and 90 age‐ and sex‐matched controls were included. All PD patients enrolled were non‐fluctuating (21 de novo, 69 treated with levodopa or dopamine agonists). PD patients and controls with Mini Mental State Examination score <23 were excluded. Psychiatric diagnosis was performed by semistructured interview according with DSM‐IV criteria and the severity of depressive and anxious symptoms was rated with clinical rating scales. Major depression was found in 21.1% PD patients vs. 3.3% controls (P < 0.01, chi‐square analysis), dystimia in 18.8% PD patients vs. 4.4% controls (P < 0.05), panic disorders in 30% PD patients vs. 5.5% controls (P < 0.01). No difference in the prevalence of other anxiety disorders was observed between the two groups. The comorbidity of mood and anxiety disorders was found in 19.3% PD patients vs. 8.6% controls (P < 0.01). No correlation was reported between the prevalence of behavioural disturbances and any of the demographic, clinical or pharmacological data taken into account. Our findings might suggest the existence of a wide spectrum of psychiatric disorders in PD ranging from pure depressive disorders, comorbid depressive and anxiety disorders, and pure anxiety disorders, presumably linked to the same neurobiological substrate.

Paroxetine in Parkinson’s disease: Effects on motor and depressive symptoms

Article abstract Selective serotonin reuptake inhibitors have been used in the treatment of depression in patients with PD. Conflicting data as to whether selective serotonin reuptake inhibitors worsen parkinsonian motor symptomatology have been reported. In this study, the additional 6 months therapy with paroxetine 20 mg/d in a group of depressed patients with PD did not modify parkinsonian motor function (Unified Parkinson’s Disease Rating Scale scores); however, in one patient, fully reversible worsening of tremor was observed. Depression, as evaluated by Beck Depression Inventory and Hamilton Depression Rating Scale, improved from baseline to final visit (p < 0.05 by analysis of variance).

SSRIs do not worsen Parkinson's disease: evidence from an open-label, prospective study.

Selective serotonin reuptake inhibitors (SSRIs) have been reported to be useful in the treatment of depression in patients with Parkinsons disease (PD). However, a few reports have suggested that SSRIs may worsen parkinsonian motor symptomatology and extrapyramidal side effects have been reported in depressed patients treated with SSRIs. So far, no prospective trial comparing the effects of different SSRIs in depressed patients with PD has been performed. The aim of the present study was to assess the effects of four SSRIs (citalopram, fluoxetine, fluvoxamine, and sertraline) on motor performance and their efficacy on depression in a group of patients with PD. Sixty-two consecutive nondemented, nonfluctuating, depressed patients with PD were included in four treatment groups (15 patiens received citalopram, 16 fluoxetine, 16 fluvoxamine, and 15 sertraline). The evaluation of extrapyramidal and depressive symptomatology was performed with use of the Unified Parkinsons Disease Rating Scale (UPDRS), Beck Depression Inventory, and Hamilton Depression Rating Scale at baseline and after 1, 3, and 6 months. Fifty-two patients completed the study. UPDRS scores were not significantly modified by the add-on therapy with each of the SSRIs studied. A significant improvement in depressive symptoms from baseline to the end of the trial was obtained with all SSRIs (Beck and Hamilton scores improving;p < 0.05 according to an analysis of variance). Our findings suggest that SSRIs do not significantly worsen extrapyramidal symptomatology and may ameliorate depression in patients with PD.

Brain-derived neurotrophic factor plasma levels in patients suffering from post-traumatic stress disorder

In both animals and humans, stress has been demonstrated to reduce the expression of the Brain-Derived Neurotrophic Factor (BDNF), a neurotrophin (NT) which promotes the proliferation, survival and differentiation of neurons. Although traumatic events have been found to be associated with lower BDNF plasma levels in affective disorders, no study has explored this parameter in patients with post-traumatic stress disorder (PTSD). We, therefore, measured BDNF plasma level in 18 patients with PTSD and in 18 healthy control subjects. Diagnoses were assessed by the Structured Clinical Interview for DSM-IV, while the specific symptoms were examined in the patients by means of the Impact of Event Scale for PTSD and the traumas experienced were assessed by using the Life Events Checklist. BDNF plasma levels were evaluated by means of a standardized Elisa method. The results, while showing significantly lower BDNF levels in PTSD patients, as compared with those of healthy subjects (p=0.001), although obtained in a small sample size, would suggest that this NT may be involved in the pathophysiology of PTSD.

Plasma Brain-Derived Neurotrophic Factor in treatment-resistant depressed patients receiving electroconvulsive therapy

There is an increasing evidence that the Brain-Derived Neurotrophic Factor (BDNF) could be involved in the mode of action of antidepressants and, perhaps, of ECT. This study aimed to investigate whether the clinical course of medication-resistant depressed patients following a course of ECT might be associated with changes of plasma BDNF concentrations. Our findings showed that at T0 (baseline) plasma BDNF levels of patients were significantly lower than those of control subjects, and that at T2 (after ECT) were significantly increased in parallel with the decrease of the Hamilton Rating Scale for Depression (HRSD) total score. However, only remitter patients who showed higher baseline BDNF levels than non-remitters reached normalized BDNF levels after ECT. These findings would suggest the potential usefulness of baseline plasma BDNF levels as predictors of response to ECT in treatment-resistant depressed patients.

DIURNAL VARIATION OF PLASMA BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) IN HUMANS: AN ANALYSIS OF SEX DIFFERENCES

Scant information is available on the diurnal variation of peripheral neurotrophic factors, including brain‐derived neurotrophic factor (BDNF), in human beings. We explored plasma and serum BDNF levels at three different clock times in a study of 28 healthy subjects of both sexes. Statistically significant diurnal variation in plasma BDNF level was detected in men, with the peak at 08:00 h and nadir at 22:00 h. At this time, the plasma BDNF concentration of men was significantly lower than that of women (p=.02). However, no diurnal variation was found either in plasma BDNF of women, in either the follicular or luteal phases of the menstrual cycle, or in serum BDNF level in both men and women. These findings support the concept of rhythmic variation in plasma BDNF regulation that seems to be sex‐related. (Author correspondence: dmarazzi@psico.med.unipi.it)

Associations between Brain-Derived Neurotrophic Factor Plasma Levels and Severity of the Illness, Recurrence and Symptoms in Depressed Patients

Background: There is increasing evidence that the brain-derived neurotrophic factor (BDNF) is involved in the pathophysiology of mood disorders and that its peripheral levels represent a reliable mirror of its concentration in the brain. The aim of the present study was to measure BDNF plasma levels in patients affected by major depression and to explore the possible relationship between the biological parameter and characteristics of the illness. Method: BDNF plasma levels were evaluated in 30 inpatients suffering from major depression, according to DSM-IV criteria, by means of a commonly employed ELISA method. The clinical characteristics were assessed by the Hamilton Rating Scale for Depression (HRSD) and the Clinical Global Impression Scale. Results: BDNF plasma levels were significantly lower in the patients with the severest illness compared with the others, and the same was true for patients with dissociative symptoms, severe sleep disturbance and recurrent depression. A significant and negative correlation was observed between the biological parameter and the retardation factor score of the HRSD. Conclusion: These findings suggest that low BDNF levels are related to both recurrence and severity of depression, as well as to symptoms typical of dysfunctions of the hypothalamic-pituitary-adrenal axis.

Relationship between bipolar illness and binge-eating disorders

In this study we describe the frequency of eating disorders (EDs) in a group of bipolar (BP) patients. We evaluated a sample of 51 outpatients, diagnosed as having BP I disorder on the basis of the Structured Clinical Interview for DSM-IV (SCID). Each of these subjects was administered the Binge Eating Disorder Clinical Interview (BEDCI) to determine the presence of binge eating disorder (BED) or bulimia nervosa (BN). Of the 51 BP patients, 14 (9 BED, 5 BN) met criteria for an ED. Most patients developed binge eating coincident with the first episode of BP disorder or after the onset of it. This was true for those who developed BED as well as BN, and involved both manic and depressive phases. All BN patients were women (5/5), and family history of binge eating was present in 80% of BN subjects, but only in 22.2% of BED and 29.7% of non-ED BP patients. We found a high frequency of concordance between BP illness and binge eating problems in our sample of BP patients. Given the temporal sequence of the mood disorder, which generally preceded the ED, we suggest a model in which the ED evolves due to modulation of emotions with food, as well as use of medications to treat BP disorder that disrupt hunger and satiety mechanisms. Given differences in gender distribution and family history, cultural and familial influences may also be significant in the minority of BP binge-eating patients who develop BN.

Pharmacokinetics and pharmacodinamics of psychotropic drugs: effect of sex

Data on the specific effects of sex on pharmacokinetics, as well as tolerability, safety, and efficacy of psychotropic medications are still meager, mainly because only recently sex-related issues have attracted a certain degree of interest within the pharmacological domain. Therefore, with the present study, we aimed to provide a comprehensive review of the literature on this topic, through careful MEDLINE and PubMed searches of the years 1990-2012. Generally, data on pharmacokinetics are more consistent and numerous than those on pharmacodynamics. Sex-related differences have been reported for several parameters that influence pharmacokinetics, such as gastric acidity, intestinal motility, body weight and composition, blood volume, liver enzymes (mainly the cytochrome P450), or renal excretion, which may alter plasma drug levels. Sex-related peculiarities may also account for a different sensitivity of men and women to side effects and toxicity of psychotropic drugs. Further, some differences in drug response, mainly to antipsychotics and antidepressants, have been described. Further studies are, however, necessary to explore more thoroughly the impact of sex on the pharmacokinetics and pharmacodynamics of psychotropic drugs, in order to reach the most appropriate and tailored prescription for each patient.

Treatment of patients with tardive dystonia with olanzapine

Tardive dystonia represents a complication of long-term use of neuroleptics and its treatment is often unsatisfactory. Atypical neuroleptics appear to improve tardive dystonia, and cases of tardive dystonia successfully managed with clozapine have been reported. The aim of this open-label video-blinded study was to evaluate the antidystonic efficacy of olanzapine, a new atypical neuroleptic with a low risk of agranulocytosis, in a group of four patients (one man and three women) with tardive cervical dystonia. They developed severe dystonia after several years of neuroleptic treatment. Extensive laboratory evaluations, as well as neurophysiologic and neuroradiologic investigations, were negative. Olanzapine was started at a dose of 5 mg/d and increased up to 7.5 mg/d. All patients were evaluated at baseline and after 2, 4, 8, and 12 weeks of treatment, using the Toronto Western Spasmodic Torticollis Rating Scale, and videotaped. At the end of the trial, the videotapes were reviewed and scored by a blind observer. A self-rating visual analog scale completed the disability evaluation.A moderate to marked improvement in dystonia was observed in all patients, and significant differences were observed in Toronto Western Spasmodic Torticollis Rating Scale scores and videotape ratings after 8 and 12 weeks of treatment compared with the basal values (p < 0.05). The average percentage of improvement in Toronto Western Spasmodic Torticollis Rating Scale score and visual analog scale was 26.4% and 42.6%, respectively. No serious side effects were reported at the maximum dosage reached (7.5 mg/d). This study warrants a larger controlled study to conclusively demonstrate the efficacy of olanzapine in tardive dystonia.