Ignazio Vecchio

Prediction of the response to citalopram and reboxetine in post-stroke depressed patients

Rationale and objectiveDepression is a significant complication of stroke. The effectiveness of antidepressant drugs in the management of post-stroke depression (PSD) has been widely investigated. However, the choice of antidepressant drug is critically influenced by its safety and tolerability and by its effect on concurrent pathologies. Here we investigate the efficacy and safety of a selective serotonin reuptake inhibitor (SSRI), citalopram, and a noradrenaline reuptake inhibitor (NARI), reboxetine, in post-stroke patients affected by anxious depression or retarded depression.MethodsThis was a randomized double-blind study. Seventy-four post-stroke depressed patients were diagnosed as affected by anxious or retarded depression by using a synoptic table. Randomisation was planned so that 50% of the patients in each subgroup were assigned for 16 weeks to treatment with citalopram and the remaining 50% were assigned to treatment with reboxetine. The Beck Depression Inventory (BDI), the Hamilton Depression Rating Scale (HDRS) and a synoptic table were used to score depressive symptoms.ResultsBoth citalopram and reboxetine showed good safety and tolerability. Citalopram exhibited greater efficacy in anxious depressed patients, while reboxetine was more effective in retarded depressed patients.ConclusionsCitalopram or other SSRIs and reboxetine may be of first choice treatment in PSD because of their good efficacy and lack of severe side effects. In addition, PSD patients should be classified according to their clinical profile (similarly to patients affected by primary depression) for the selection of SSRIs or reboxetine as drugs of choice in particular subgroups of patients.

The SSRI, citalopram, improves bradykinesia in patients with Parkinson's disease treated with L-dopa.

Idiopathic Parkinsons disease (IPD) is characterized by motor signs such as akinesia, rigidity, and often tremor at rest. In addition to these symptoms, depression is a common finding affecting 40% of patients with IPD. This study evaluates the effect of the selective serotonin reuptake inhibitor, citalopram, on motor and nonmotor symptoms of depressed and nondepressed patients with IPD. Forty-six nondemented patients with IPD (24 men, 22 women; mean age 64 ± 5.3 years; mean ± SD disease duration, 6.4 ± 3.2 years; mean ± SD Hoehn-Yahr stage, 2.8 ± 1.2) were included in the study. Patients were divided in two subgroups: depressed (n = 18) and nondepressed (n = 28). Citalopram was added in an unblinded manner, starting with 10 mg/d, and, after a week, increased up to 20 mg/d in the depressed subgroup (n = 18) and in half of the nondepressed subgroup (n = 14). Parkinsonian and depressive symptoms were evaluated before and after 1 and 4 months of treatment. Statistical evaluation was made by analysis of variance for repeated measures. Citalopram did not worsen motor performance in IPD, but improved bradykinesia and finger taps after 1 month and 4 months of treatment both in patients with and without depression (p < 0.05 versus baseline). A clear improvement in mood was also observed in 15 of 16 patients with depression. Although case reports indicate that citalopram can potentially worsen the motor symptoms in patients with PD, to date this effect has not been confirmed. Many of the symptoms, typically associated with depression, can be observed in nondepressed patients with IPD, because signs thought to represent depression can be produced by Parkinsons disease. In this study, we observed that when combined with levodopa, citalopram induces an improvement of motor performance, in particular of subscores 23 and 31 of Unified Parkinsons Disease Rating Scale both in depressed and in nondepressed patients with IPD.

Different clinical and evolutional patterns in late idiopathic and vascular parkinsonism.

AbstractObjectiveThe aim of this study was to examine the clinical picture of Parkinson’s disease (PD) and vascular parkinsonism (VP) in the elderly, in an attempt to differentiate the clinical history, symptoms, signs and response to therapy.Material and methodsThirty–two elderly patients with late onset PD and 45 with VP were enrolled and the clinical features of two groups were compared. All patients underwent brain MRI and were scored using the Unified Parkinson’s Disease Rating Scales (UPDRS) –II, –III.ResultsPatients with PD had a younger age at onset and a longer duration of the disease as compared to patients with VP. Nearly all PD patients showed a good response to levodopa therapy, while only 29% of patients with VP were responsive to levodopa treatment. Vascular risk factors as well as postural tremor, gait disorders and pyramidal signs with lower body predominance, were more frequent in patients with VP. Ninety–three % of PD patients had normal MRI, whereas all patients with VP had cerebral vascular lesions. UPDRS–II, –III scores at baseline were higher in VP than in PD patients and their increases throughout the follow–up period were more marked in VP than in PD patients.ConclusionsClinical history, symptoms, signs, response to therapy, and brain imaging help to differentiate PD and VP as two clinical entities with different clinical, prognostic and therapeutic implications, even if the coexistence of PD and a cerebral vascular disease in elderly patients is not infrequent and can make the diagnosis difficult.

Evaluation of the Prophylactic Efficacy of Amitriptyline and Citalopram, Alone or in Combination, in Patients with Comorbidity of Depression, Migraine, and Tension-Type Headache

Antidepressants are used to treat chronic daily headache disorders such as migraine and chronic tension-type headache (TTH), which are often associated with depression and anxiety. Here, we studied the efficacy and tolerability of amitriptyline and citalopram, given alone or in combination, in patients with ‘triple’ comorbidity of depression, TTH, and migraine. Eighty-eight patients were enrolled in the study and randomly divided into two groups. The first group received amitriptyline and the second citalopram for 16 weeks. Patients were assessed at weeks 0, 4, 8, and 16. The two drugs were equally efficacious in relieving depressive symptoms, although amitriptyline was more efficacious than citalopram in reducing migraine and TTH attacks. Patients who did not respond to monotherapy (<30% of improvement in the clinical scores) were treated with a combination of the two drugs for 16 additional weeks. In these selected patients, the combined treatment produced a substantial improvement in depression, migraine and TTH without producing major side effects such as those commonly related to the ‘serotonergic’ syndrome. The results indicate that a combined therapy with amitriptyline and citalopram may be particularly beneficial for patients with TTH, migraine and comorbid depression that do not respond to monotherapy.

Trazodone therapy of the post-stroke depression

The incidence of depression following a hemispheric stroke ranges from 25 to 60%. The benefit of antidepressant therapy on the outcome of rehabilitation in the subacute post-stroke phase is well known. We studied subjects both with and without evidence of depression, as indicated by any one of three criteria: (i) Clinical diagnosis of depression, (ii) Abnormal Zung-depression score. (iii) Abnormal dexamethasone suppression test (DST). Patients in a stroke rehabilitation program (22) were randomized to receive either placebo or 300 mg/day trazodone-HCl, beginning 30 days after the stroke. Patients with either a clinical diagnosis of depression or abnormal Zung depression scores showed a consistent trend towards greater improvement in Barthel activities of daily living (ADL) scores, with antidepressant therapy, as compared to patients receiving placebo. An abnormal DST was associated with significant improvement in the ADL scores in subjects receiving trazodone, i.e., in post-stroke depression such a treatment seems to be beneficial.

Gerstmann-Sträussler-Scheinker disease with P102L-V129 mutation: a case with psychiatric manifestations at onset.

Gerstmann-Sträussler-Scheinker disease (GSS) is an adult onset, rare, genetically determined autosomal dominant prion disease. Clinically, it is characterized predominantly by slowly progressive spino-cerebellar dysfunction with ataxia, absent reflexes in the legs and cognitive impairment. Onset is usually in the fifth decade and in the early phase, ataxia is predominant. Mutations in the prion protein gene (PRNP) had been identified and the most important of these is at codon 129. A genotype-phenotype relationship with genetic polymorphism at residue 129 between methionine and valine has been supposed. We describe a patient with GSS and P102L-V129 mutation in which the onset with prominent psychiatric features characterized by apathy and depression and not with cerebellar sign and the clinical course with seizures, nor observed in P102L-V129 cases, allow us to confirm observations that the GSS caused by the 102 mutation is influenced by the codon 129 polymorphism with a specific genotype-phenotype influence, but probably other additional factors might be considered as background for phenotypic variability.

Branched chain amino acids supplemented with L-acetylcarnitine versus BCAA treatment in hepatic coma: a randomized and controlled double blind study.

Objective Our earlier study has demonstrated that the administration of L-acetylcarnitine (LAC) improves neurological symptoms and serum parameters in hepatic coma. The aim of this work has been to evaluate the efficacy of the LAC and branched chain amino acids (BCAA) versus BCAA, administered in intravenous infusion, in patients with cirrhotic hepatic coma. Methods Forty-eight highly selected patients were enrolled in the study and, after randomization, received blindly LAC+BCAA (n=24) versus BCAA (n=24). The two groups were similar in age, sex, pathogenesis of cirrhosis, and severity of liver disease. The comparison between values before and after LAC planned treatment showed statistical significant differences in neurological findings, evaluated by the Glasgow Scale, ammonia serum levels, blood urea nitrogen, and EEG. Results After 60 min of the study period, the LAC+BCAA treated patients compared with BCCA treated showed a significant decrease of ammonia serum levels: 41.20 versus 10.40 μmol P<0.05. After 1 day of the study period, the LAC+BCAA treated patients compared with BCCA treated patients showed a significant increase of Glasgows score: 3.60 versus 1.50 score P<0.05; a significant decrease of ammonia serum levels: 63.30 versus 27.00 μmol P<0.01; a significant improvement of EEG cps/s: 2.70 versus 0.6 P<0.001. No side-effects were observed in our study series. Conclusion Our study demonstrated that the administration of BCAA supplemented with LAC might improve neurological symptoms and serum ammonium levels in selected cirrhotic patients with hepatic coma.

Autoimmune thyroiditis and acquired demyelinating polyradiculoneuropathy.

Guillain-Barrè syndrome (GBS) and Miller-Fisher syndrome (MFS) are variant forms of acquired demyelinating polyradiculoneuropathy. Their concurrence with immune disorders of the thyroid is infrequent. We report on a 7.5-year-old girl in whom a subclinical thyroiditis was concurrently detected to GBS and a 70-year-old woman with Hashimotos thyroiditis (HT) who had recurrent MFS. Even though autoimmune thyroiditis is associated with many autoimmune disorders more often than would be expected by chance alone, its concurrence with immune disorders of the peripheral nerve is less frequently reported. The calculated coincidental concurrence of acquired demyelinating polyradiculoneuropathy (in both variants, MFS and GBS) and autoimmune thyroiditis (as in the present cases) was extremely low (0.0004%), thus suggesting common pathogenic mediators.

Modulatory action of noradrenergic system on spinal motoneurons in humans.

Previous findings in animals demonstrated that the noradrenergic coeruleospinal system exerts a tonic facilitation on spinal reflexes and that activation of alpha2-autoinhibitory receptors can be responsible for a disfacilitation of the spinal activity. To investigate this issue further, we examined whether this system is also involved in descending facilitatory control of spinal motoneurons in healthy humans. The H-reflex technique was utilized to assay the motoneuronal excitability. The ratio between the maximal reflex response (H) and maximal direct response (M) was determined in each subject and was calculated at 10 min intervals before and after i.v. administration of the alpha2-agonist clonidine (0.5 microg/kg). In all subjects a marked decrease of the H/M ratio, due to depression of the H response, occurred 10 min following the clonidine injection and reached its maximum within 30 min. No significant changes of blood pressure values were provoked by drug injections. These results suggest that an autoinhibitory action may be induced by alpha2-receptor activation of locus coeruleus neurons in humans, and that this device may serve as a mechanism for a myotonolytic action on spinal motoneurons.

Is it safe to use antidepressants after a stroke

Depression is an important complication of stroke. Although antidepressants are widely used for the treatment of poststroke depression (PSD), prescription is critically influenced by their safety, tolerability and by the impact on co-morbidities. The authors reviewed the literature on the use of antidepressants after stroke. Selective serotonin re-uptake inhibitors are effective and have a good profile of safety and tolerability in PSD. They are, therefore, used as first-line drugs in the treatment of PSD, although potential cardiovascular and cerebrovascular effects, drug–drug interactions and intolerability in a minority of patients have to be considered. Other antidepressants appear to be safe and effective in selected patients. PSD patients should be classified according to their clinical profile for the selection of the drug of choice in particular sub-groups of patients.