Effect of nortriptyline and paroxetine on extrapyramidal signs and symptoms: A prospective double-blind study in depressed elderly patients.

Selective serotonin-reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) have been reported to induce extrapyramidal signs and symptoms (EPS). The authors examined the change from baseline EPS, measured by an objective rating scale, in a group of elderly depressed patients participating in an ongoing randomized, double-blind comparison of nortriptyline and paroxetine. Mild baseline EPS were present in both groups. After 6 weeks of antidepressant treatment, patients in the nortriptyline group showed a significant decrease in total EPS scores. Patients in the paroxetine group showed a similar decrease in EPS from baseline, which did not reach statistical significance. There was no significant difference between nortriptyline and paroxetine in the change in EPS.     

Longitudinal analysis of nortriptyline side effects in elderly depressed patients.

Forty-five depressed elderly patients were closely monitored in a research setting during treatment with nortriptyline and interpersonal psychotherapy for 7 consecutive months of acute and continuation treatment. Overall, nortriptyline was efficacious and well tolerated in this group. The frequency of somatic complaints measured by the Rating Scale for Side Effects declined by 50% during the acute phase of treatment, suggesting that many somatic complaints that may be attributed to side effects of nortriptyline are actually somatic symptoms of depression. The authors discuss the implications of these findings and offer practical advice for the treating clinician.     

Double-blind, randomized comparison of mirtazapine and paroxetine in elderly depressed patients.

OBJECTIVE: Authors studied the efficacy and tolerability of mirtazapine and paroxetine in elderly patients with major depression during an acute phase (8 weeks) and an extension phase (16 weeks). METHODS: Patients with major depression and without dementia, at least 65 years old, were eligible; they were randomized to mirtazapine or paroxetine once daily, with doses increasing over 42 days. Efficacy was assessed with the Ham-D and Clinical Global Impressions Scale, and tolerability was assessed from adverse events. RESULTS: Of 255 patients randomized, 126 on mirtazapine and 120 on paroxetine were included in the efficacy analysis. Differences favoring mirtazapine were observed for the mean change from baseline in Ham-D-17 score. Other significant differences were in the proportion of patients classified as responders (50% decrease from baseline Ham-D-17 scores) at Day 14 and in remission (Ham-D-17 score of 7 or less) at Day 42. The median time to response was 26 days in the mirtazapine group and 40 days in the paroxetine group. The mirtazapine group also showed more reduction in Ham-D Factor I (Anxiety/Somatization) and Factor VI (Sleep Disturbance) scores. Efficacy of both drugs was maintained during the extension phase. Patients on paroxetine were more likely to discontinue therapy in the acute phase because of adverse events. CONCLUSION: During the first weeks of treatment, antidepressant effects were more pronounced in the mirtazapine group, suggesting that mirtazapine has an earlier onset of action. Mirtazapine also demonstrated a better tolerability profile and represents a valuable option for the treatment of depression in elderly patients.     

Effects of nortriptyline and paroxetine on QT variability in patients with panic disorder

This study investigated beat-to-beat QT variability in patients with panic disorder before and after treatment with nortriptyline (n = 13) and paroxetine (n = 16), using an automated algorithm to compute QT intervals. An increase in QT variability appears to be associated with symptomatic patients with dilated cardiomyopathy and also with an increased risk for sudden cardiac death. QTvi (QT variability index: a log ratio of QT variance normalized for mean QT over heart rate variability normalized for mean heart rate) was significantly higher in supine posture in patients with panic disorder treated with nortriptyline (P = 0.006) but not paroxetine. Thus paroxetine may be a better drug of choice especially in patients with coexisting cardiac disease. These findings are important especially in view of the recent reports of increased risk for cardiovascular mortality and sudden death in patients with anxiety and depression. QTvi can be a valuable noninvasive measure of temporal repolarization lability, especially to study the side effects of medications which affect cardiac autonomic function.     

Weight change in older depressed patients during acute pharmacotherapy with paroxetine and nortriptyline: a double-blind randomized trial.

The authors examined weight change in 32 elderly patients treated for 12 weeks with either nortriptyline or paroxetine during acute-phase pharmacotherapy. Random assignment to treatment and double-blind assessment of weight change were performed, including ascertainment of premorbid (i.e., pre-depression) weight. Pretreatment severity of depression was correlated with weight loss during the depressive episode and depression-related weight loss, in turn, correlated with weight regained during antidepressant treatment. There was no differential weight change associated with nortriptyline vs. paroxetine. Rather, subjects in both groups approximated their premorbid weights by 12 weeks of acute-phase pharmacotherapy with either agent. However, additional investigation of weight change during continuation and maintenance pharmacotherapy is necessary and would be clinically useful for the long-term management of elderly patients with depression.     

A placebo-controlled comparison of nortriptyline and phenelzine in maintenance therapy of elderly depressed patients

Fifty-one elderly depressed outpatients who had responded to antidepressants and completed continuation therapy were observed under double-blind conditions for 1 year. Twenty-three had been switched to placebo, while 13 and 15 took nortriptyline hydrochloride and phenelzine sulfate, respectively. Patients administered phenelzine did significantly better with 13.3% recurrences than patients administered either nortriptyline (53.8% recurrences) or placebo (65.2% recurrences). In addition, patients who had higher Hamilton scores and who had an earlier age of onset of the first depressive episode were significantly more likely to have recurrences.     

A twelve-week, double-blind, randomized comparison of nortriptyline and paroxetine in older depressed inpatients and outpatients.

Selective serotonin reuptake inhibitors may be less efficacious than tricyclic antidepressants in the treatment of severe depression in older patients. The authors compared the 12-week clinical outcome of older depressed patients treated with nortriptyline or paroxetine in a double-blind randomized comparison in 116 psychiatric inpatients and outpatients (mean age: 72+/-8 years) who presented with a major depressive episode or melancholic depression. Discontinuation and response rates were compared in patients who began or who completed treatment. The discontinuation rate due to side effects was significantly higher with nortriptyline than with paroxetine (33% vs. 16%). There were no significant differences between the rates of response in the Intent-to-Treat analysis (nortriptyline: 57% vs. paroxetine: 55% ), or the Completer analysis (nortriptyline: 78% vs. paroxetine: 84%). Although paroxetine appears to be better tolerated than nortriptyline, the efficacy of these two drugs does not appear to differ in the acute treatment of older depressed patients, including hospitalized patients and those with melancholic features.     

Effects of paroxetine or milnacipran on serum brain-derived neurotrophic factor in depressed patients

Brain-derived neurotrophic factor (BDNF) is an important member of the neurotrophin family of growth factors, abundant in the brain and periphery. Researchers have reported that serum BDNF levels in drug-free depressed patients are lower than those of healthy controls, and have proposed that these low levels might reflect a failure of neuronal plasticity in depression. In the present study, we investigated the effects of paroxetine, an SSRI, and milnacipran, an SNRI, on serum BDNF levels in depressed patients. Serum levels of BDNF were measured by ELISA before, 4 weeks, and 8 weeks after the start of treatment with antidepressants. Forty-two patients were randomly administered paroxetine (21 cases) or milnacipran (21 cases). A negative correlation was found between serum BDNF levels and baseline Ham-D scores. The response and remission rates for each drug were not significantly different. Serum BDNF levels in responders were significantly increased 2.6- and 1.8-fold 8 weeks after treatment with paroxetine or milnacipran, respectively. These results suggest that both drugs improve the depressive state by increasing BDNF levels.     

Plasma levels and effects of nortriptyline in geriatric depressed patients

Pharmacokinetic, therapeutic effects, and side effects of nortriptyline were studied in geriatric depressed patients treated with a standard dose of 150 mg/day. Plasma levels and elimination half-life of nortriptyline were no different in geriatric patients than younger patients. The antidepressant therapeutic effects of nortriptyline appeared to be similar in geriatric patients as in younger depressed patients. Geriatric patients experienced few subjective side effects of nortriptyline. Overall, the drug produced no clinically significant changes in several parameters of the EKG, and no geriatric patient experienced tachycardia on nortriptyline. Nortriptyline did induce significant orthostatic hypotension in the systolic component, but not in the diastolic component. However, the orthostatic hypotension produced by nortriptyline was not greater in geriatric patients than in younger patients treated with the same dose.     

Treatment of major depression with nortriptyline and paroxetine in patients with ischemic heart disease.

OBJECTIVE: This study compared the efficacy, tolerability, and safety of paroxetine and nortriptyline in depressed patients with ischemic heart disease. METHOD: After a 2-week, single-blind placebo lead-in phase, 81 outpatients with DSM-III-R-defined nonpsychotic unipolar major depression and ischemic heart disease were randomly assigned to double-blind treatment with paroxetine or nortriptyline for 6 weeks. Paroxetine was administered at a fixed-flexible dose of 20-30 mg/day. Nortriptyline dose was adjusted with the use of blood-level monitoring to reach a plasma concentration of 50-150 ng/ml. RESULTS: Twenty-seven of the 41 patients who started treatment with paroxetine and 29 of the 40 patients who started treatment with nortriptyline had an improvement of at least 50% in their Hamilton Depression Rating Scale scores. Significantly more patients taking nortriptyline discontinued treatment prematurely (35% versus 10%), and more patients taking nortriptyline had adverse events resulting in termination (25% versus 5%). CONCLUSIONS: Both treatments were efficacious. Sixty-three percent of all patients improved at least 50%, and of these, 90% met the criteria for remission. Paroxetine was better tolerated than nortriptyline and less likely to produce cardiovascular side effects.     

A biofeedback study of postural sway.

An experiment was performed to control postural sway under auditory and visual feedback signals using a new apparatus. The subjects of 52 healthy high school girls were divided into 13 small groups. Each small group had four subjects who were assigned to one of the following four groups; 1) visual feedback group, 2) auditory feedback group, 3) auditory and visual feedback group, and 4) control group. Comparisons were made as to the duration of the green lamp being on, which indicated sway stayed around the initial central gravity. The results showed that auditory and visual feedback groups had a significant increase in the duration as compared to other three groups. With regard to the changes in the areas of postural sway, the largest increase was seen in the auditory and visual group. While the three feedback groups showed downward curves, the control group showed an upward one. Thus it is suggested that postural sway can be voluntarily controlled by a combination of an auditury feedback procedure and a visual feedback procedure, but not be either of them independently.     

Platelet counts in depressed patients treated with amitriptyline or paroxetine.

OBJECTIVE: To assess whether therapy with two widely used antidepressants influences platelet counts. SUBJECTS AND METHODS: In 90 patients hospitalized for treatment of a major depressive episode according to DSM-IV, platelet counts were performed after a 6 d antidepressant-free run-in period and again after 35 d of active standardized treatment with amitriptyline (n = 40) or paroxetine (n = 50). RESULTS: There was a trend for platelet counts to increase during treatment with amitriptyline (from 245.5 +/- 68.6 to 256.8 +/- 69 cells x 10(9) L(-1), P < 0.06); no change was observed during treatment with paroxetine (from 232.6 +/- 58.3 to 234.6 +/- 68.9 cells x 10(9) L(-1), n.s). CONCLUSION: Treatment with amitriptyline tends to be associated with elevated platelet counts. The cause for this increase is not known, but may be relevant in terms of patients' long-term thromboembolic risk.     

Effects of deep brain stimulation and levodopa on postural sway in Parkinson's disease

OBJECTIVE: To quantify postural sway in subjects with Parkinson's disease and elderly controls, and determine the effects of Parkinson's disease, deep brain stimulation, levodopa, and their interactions on postural control during quiet stance. METHODS: Centre of foot pressure (CoP) displacement under each foot was measured during three 60 s trials of quiet stance with eyes open in 11 controls and six patients with Parkinson's disease. Subjects with Parkinson's disease were tested in four treatment conditions: off both deep brain stimulation and levodopa (off condition); on deep brain stimulation; on levodopa; and on both deep brain stimulation and levodopa. The variables extracted from CoP included: root mean square distance (rms), mean velocity, 95% power frequency (f(95%)), area of the 95% confidence ellipse (ellipse area), direction of its major axis (mdir), and postural asymmetry between the feet. RESULTS: rms and area of postural sway were larger than normal in subjects with Parkinson's disease in the off condition, increased further with levodopa, and significantly decreased with deep brain stimulation. Mean velocity and f(95%) were also larger than normal but were restored to normal by all treatments, especially by deep brain stimulation. The combined effect of deep brain stimulation and levodopa resulted in a postural sway that was an average of the effect of each treatment individually. Levodopa increased sway more in the mediolateral than in the anterior-posterior direction. Subjects with Parkinson's disease had asymmetrical mean velocity and f(95%) between the feet, and this asymmetry increased with levodopa but decreased with deep brain stimulation. The f(95%) of the CoP correlated with tremor, posture, and gait subcomponents of the unified Parkinson's disease rating scale. CONCLUSIONS: Subjects with Parkinson's disease have abnormal postural sway in stance. Treatment with levodopa increases postural sway abnormalities, whereas treatment with deep brain stimulation improves postural sway. Quantitative evaluation of static posturography may be a useful adjunct to clinical measures in patients with Parkinson's disease.     

Quantification of postural sway in normals and patients with cerebellar diseases

Posturography was performed in 41 patients with cerebellar diseases by means of a force measuring platform using an on-line computer program which calculated sway path, sway area, antero-posterior and lateral sway components and the amount of visual stabilization. Postural ataxia was quantitatively studied in 8 patients with spinal ataxia (Friedreich's), 6 patients with vestibulocerebellar lesions, 11 patients with anterior lobe atrophy, 7 patients with hemispheral cerebellar lesions, and 9 patients with a disease affecting all parts of the cerebellum. Patients with lesions of the cerebellar hemispheres could not be separated from normals by means of posturography. Lesions of the spino-cerebellar afferents (Friedreich' ataxia) caused an omnidirectional low frequency sway with preserved visual stabilization. Patients with anterior lobe atrophy showed a predominant antero-posterior sway, often with a spontaneous high frequency body tremor around 3 Hz. Vestibulo-cerebellar lesions exhibited omnidirectional low frequency sway poorly stabilized by vision. Quantitative posturography helps to localize cerebellar lesions and allows for quantitative follow-up studies of cerebellar diseases.     

Dose and plasma levels of nortriptyline and chlorpromazine in delusionally depressed adolescents and of nortriptyline in nondelusionally depressed adolescents

Eight adolescents with major depressive disorder were treated with nortriptyline and six adolescents with delusional depression were treated with combined nortriptyline and chlorpromazine. Dose and plasma levels of nortriptyline for the two groups were compared. The delusional group receiving combined drug treatment needed significantly less nortriptyline than did the nondelusional group receiving only nortriptyline to obtain similar mean steady state plasma levels of the drug. The mean plasma chlorpromazine levels were quite low.     

Nortriptyline response in elderly depressed patients.

1. Depressed geriatric patients were treated with nortriptyline (NT) for 6 weeks. The authors measured serum levels of NT and 10-hydroxynortriptyline (10-OH-NT) using a column-switching HPLC method, and examined aging effects on NT steady-state levels to NT doses (doses/kg) ratios and NT levels to 10-OH-NT levels ratios as well as clinical response and propensity for side effects. 2. There was no significant relationship between the ages and the NT serum levels to NT doses (doses/kg) ratios, the ages and the 10-OH-NT levels to NT levels ratios, or the ages and the clinical response or the %improvement of Hamilton Scores. 3. Then the authors divided the subjects into two groups: a younger group and an elderly group with the cut off age of 60. The elderly group received significantly smaller doses of NT and had significantly lower serum levels of NT. The elderly group had tendency to have lower serum levels of 10-OH-NT. However, no significant difference was found in the improvement scores or the %improvement of depression. The elderly patients did not have higher propensity for unnegligible side effects.     

Effect of paroxetine on thyroid hormone levels in severely depressed patients

There are very divergent appraisals of the effect of antidepressants on thyroid parameters and their possible correlation with the response. Whereas there are numerous investigations of tricyclic antidepressants, so far, there are only limited data on the possible effect of serotonin-selective reuptake inhibitors on neuroendocrine parameters. The present study showed a significant reduction of 11. 2% in thyroxine during treatment with 20 mg paroxetine in 25 severely depressed patients.