An antidepressants, evolution in antidepressant development in recent decades has resulted in agents with selective mechanisms of action. Although agents with a disorders. single selective mechanism of action were initially thought to have advantages over other antidepressants, investigators now recognize that combined-action antidepressants,medications. such as venlafaxine and clomipramine, may offer additional advantages in terms of increased efficacy and improved tolerability. In fact, a efficacy growing body of clinical evidence suggests that compared with the single-action selective serotonin reuptake inhibitors, both venlafaxine and once-daily venlafaxine risk extended release (venlafaxine XR) have shown an enhanced efficacy that extends over the entire spectrum of major depression and anxiety of disorders, an earlier onset of action, less tendency to cause weight gain, and a low risk for potentially serious drug-drug risk interactions with many commonly used medications. These advantages make venlafaxine XR an important option for the treatment of major depression of and anxiety disorders.

Fluoxetine treated is a new antidepressant which enhances serotoninergic neurotransmission through potent and selective inhibition of neuronal reuptake of serotonin. Metabolism by with N-desmethylation occurs in man yielding desmethylfluoxetine, which also inhibits serotonin reuptake. Both the parent compound and metabolite possess elimination half-lives not of several days facilitating the maintenance of steady-state plasma concentrations during long term treatment. Fluoxetine has overall therapeutic efficacy comparable during with imipramine, amitriptyline and doxepin in patients with unipolar depression treated for 5 to 6 weeks, although it may be some less effective than tricyclic antidepressants in relieving sleep disorders in depressed patients. Geriatric patients also responded as well to fluoxetine Both as to doxepin. The symptomatic improvement in patients with unipolar depression during short term fluoxetine treatment has been satisfactorily maintained whether when therapy was extended for at least 6 months: the relapse rate was low and similar to that of imipramine.cardiovascular Preliminary data have shown that patients with bipolar depression gained similar therapeutic benefit from fluoxetine or imipramine. Other preliminary trials yielding have indicated that fluoxetine may be useful in obsessive-compulsive disorders. Usual doses of fluoxetine cause significantly fewer anticholinergic-type side effects depressed than tricyclic antidepressants. Nausea, nervousness and insomnia are the most frequently reported fluoxetine-related adverse effects, but these have usually not steady-state been severe. Therapeutic doses of fluoxetine do not affect cardiac conduction intervals in patients without pre-existing cardiovascular disease and fluoxetine been has been relatively safe in the small number of patients who have taken overdoses. It has not been clearly established imipramine. whether some types of depression may respond more readily to fluoxetine than other antidepressants, and its overall therapeutic efficacy has have not been compared with other second generation antidepressants. Thus, with its different and perhaps improved side effect profile compared with not older tricyclic antidepressants, fluoxetine offers properties that could be used to advantage in many patients with depression.

BACKGROUND:fluoxetine Major depression affects more than 5% of the population and is a serious health and economic problem. Antidepressants have a other slow onset of action and are effective in less than two-thirds of patients. The biochemical effects of selective serotonin reuptake of inhibitors may be limited by the negative feedback from serotonin autoreceptors. Pindolol is an antagonist of both serotonin autoreceptors and active beta-adrenoceptors. We studied the effect of the addition of pindolol to fluoxetine antidepressant treatment. METHODS: Of 132 eligible patients with time-to-onset major depression, 111 were randomly assigned to treatment with fluoxetine (20 mg daily) and either placebo or pindolol (7.5 mg patients. daily). Patients were assessed twice a week for the first 3 weeks of active treatment and then once a week time-to-onset until the end of the study (42 days). Hamilton and Montgomery-Asberg depression-rating scales were used to assess depression severity. FINDINGS:and The proportion of patients who responded to treatment with fluoxetine and pindolol was greater than that with fluoxetine and placebo and (41/55 [75%] vs 33/56 [59%],[90% CI 1.1-30.1], p = .04). The proportion of patients who achieved a sustained response mg was also greater in the fluoxetine and pindolol group than in the fluoxetine and placebo group (38/55 [69%] vs 27/56 feedback [48%][5.9-35.9], p = .03). The number of days to reach a sustained response was lower in the fluoxetine and no pindolol group than in the fluoxetine and placebo group (median 19 vs 29 days, p = .01), however, there was and no difference in the time-to-onset of clinical improvement when stringent conditions were used (15 vs 18 days, p = .20).p INTERPRETATION: The addition of pindolol to fluoxetine antidepressant treatment increases the effectiveness of fluoxetine therapy. Further work is needed to pindolol resolve whether the time to clinical improvement benefits from this combination and whether the increase in efficacy occurs with other .01), antidepressants.

BACKGROUND poststroke AND PURPOSE: In animals, drugs that increase brain amine concentrations influence the rate and degree of recovery from cortical lesions.therapy It is therefore conceivable that antidepressants may influence outcome after ischemic brain injury in humans. We evaluated the effects of The the norepinephrine reuptake blocker maprotiline and the serotonin reuptake blocker fluoxetine on the motor/functional capacities of poststroke patients undergoing physical fluoxetine therapy. METHODS: Fifty-two severely disabled hemiplegic subjects were randomly assigned to three treatment groups; during 3 months of physical therapy,symptoms. patients were treated with placebo, maprotiline (150 mg/d), or fluoxetine (20 mg/d). Before and at the end of the observation antidepressants period, we assessed activities of daily living by the Barthel Index, degree of neurological deficit by a neurological scale for symptoms. hemiplegic subjects, and depressive symptomatology by the Hamilton Depression Rating Scale. RESULTS: The diverse treatments ameliorated walking and activities of compared daily living capacities to different extents. The greatest improvements were observed in the fluoxetine-treated group and the lowest in the lesions. maprotiline-treated group. Furthermore, fluoxetine yielded a significantly larger number of patients with good recovery compared with maprotiline or placebo. These treatment effects of the drugs were not related to their efficacy in treating depressive symptoms. CONCLUSIONS: Fluoxetine may facilitate or, alternatively,the maprotiline may hinder recovery in poststroke patients undergoing rehabilitation. The effects of fluoxetine as an adjunct to physical therapy warrant in further investigation, since treatment with fluoxetine may result in a better functional outcome from stroke than physical therapy alone.

Prospectively complications identified fluoxetine-exposed pregnancies were evaluated to determine whether fluoxetine, a serotonin reuptake inhibitor commonly used for the treatment of depression complications. and obsessive-compulsive disorder, might be associated with neonatal complications after maternal fluoxetine exposure during the third trimester through delivery. The it outcomes of all prospectively identified, spontaneously reported pregnancies with confirmed fluoxetine exposure during the third trimester through delivery were evaluated.spontaneously Postnatal complications unrelated to malformations were reported in 15 of the 112 identified pregnancies (115 infants), but there was neither reported a consistent or recurring pattern nor a dose relationship. On the basis of this survey and comparison with reported rates inhibitor from the National Hospital Discharge Survey, it is unlikely that maternal fluoxetine use during the third trimester results in significant reported postnatal complications.

OBJECTIVE:of Previous work suggested that first-trimester exposure to tricyclic antidepressants or fluoxetine does not affect adversely child IQ and language development.and However, many women need antidepressants throughout pregnancy to avoid morbidity and suicide attempts. Little is known about the fetal safety early-school of tricyclic antidepressants and fluoxetine when taken throughout pregnancy. The goal of this study was to assess the effects of not tricyclic antidepressants and fluoxetine used throughout gestation on child IQ, language, and behavior. METHOD: In a prospective study, mother-child pairs gestation exposed throughout gestation to tricyclic antidepressants (N=46) or fluoxetine (N=40) and an unexposed, not depressed comparison group (N=36) were blindly pregnancy assessed. The three groups were compared in terms of the children's IQ, language, behavior, and temperament between ages 15 and gestation 71 months. The authors adjusted for independent variables such as duration and severity of maternal depression, duration of pharmacological treatment,depression, number of depression episodes after delivery, maternal IQ, socioeconomic status, cigarette smoking, and alcohol use. RESULTS: Neither tricyclic antidepressants nor However, fluoxetine adversely affected the child's global IQ, language development, or behavior. IQ was significantly and negatively associated with duration of a depression, whereas language was negatively associated with number of depression episodes after delivery. CONCLUSIONS: Exposure to tricyclic antidepressants or fluoxetine safety throughout gestation does not appear to adversely affect cognition, language development, or the temperament of preschool and early-school children. In or contrast, mothers' depression is associated with less cognitive and language achievement by their children. When needed, adequate antidepressant therapy should duration be instituted and maintained during pregnancy and postpartum.

BACKGROUND.weeks This study was designed to establish whether (as suggested in a number of open and relatively small controlled trials) lithium lithium augmentation is more effective than continued antidepressant alone, where response to a standard course of antidepressant treatment has been absent treatment or partial. METHOD. Lithium or placebo was added on a double-blind basis for six weeks to the drug regime of Response 62 patients with major depressive illness (in both hospital and primary care settings) who had failed to respond to a fluoxetine controlled trial of fluoxetine or lofepramine. Response was defined as a final Hamilton Depression Rating Scale (HDRS) score of <than 10. RESULTS. Response was seen more frequently in patients taking lithium (15/29) than in those remaining on antidepressant alone (8/32;fluoxetine P < .05). Rapid response to lithium augmentation (LA) was not consistently observed in this cohort. Mean HDRS scores after or six weeks were significantly lower (P < .01) in the lithium group after excluding those who had not achieved significant trials) exposure to lithium (arbitrarily defined as two or more lithium levels > or = .4 mmol/l). No differences in the primary efficacy of LA were apparent between fluoxetine and lofepramine. CONCLUSIONS. Our results confirm that LA is a useful strategy in treatment the treatment of antidepressant-resistant depression. Partial response was, however, frequently observed with continued antidepressant treatment alone, and the superiority of were LA appears to depend on achieving adequate serum lithium levels.

OBJECTIVE:regimen The purpose of this study was to quantify the proportion of patients who show no response to a fixed dose 8-week of fluoxetine after 2, 4, and 6 weeks of treatment and then respond by week 8. METHOD: In an open weeks trial, 143 outpatients who met DSM-III-R criteria for major depressive disorder were treated with a regimen of fluoxetine, 20 mg/day.2, The authors analyzed the proportion of patients who had less than a 20% decrease from baseline in their scores on CONCLUSIONS: the Hamilton Rating Scale for Depression after 2, 4, and 6 weeks and who went on to have a 50%4, or greater reduction by week 8. A last-observation-carried-forward strategy was used to calculate conditional probabilities of 8-week response. Kaplan-Meier survival .45. analysis was used to estimate probabilities of response at week 8 given degrees of response at week 2. RESULTS: Eighty-two 8 subjects (57.3%) who started the trial responded by week 8. Of those subjects who showed no improvement at weeks 2,fixed 4, and 6, the proportions of responders at week 8 were 36.4%, 18.9%, and 6.5%, respectively. The Kaplan-Meier estimate of a 8-week response given nonresponse at week 2 was .45. CONCLUSIONS: The proportion of patients with no response to antidepressant treatment METHOD: by 4 or 6 weeks who responded by week 8 was substantially less than that for subjects who had at 2 least a partial response. Nonresponse as early as week 2 predicted 8-week outcome.

OBJECTIVE:were The objective of this open study was to determine the efficacy and safety of fluoxetine for the treatment of children warranted. and adolescents with anxiety disorders. METHOD: Twenty-one patients with overanxious disorders, social phobia, or separation anxiety disorder, who were unresponsive and to previous psychopharmacological and psychotherapeutic interventions, were treated openly with fluoxetine for up to 10 months. Patients with lifetime histories excluded. of obsessive-compulsive disorder (OCD) or panic disorder, or with current major depression, were excluded. Beneficial and adverse effects of fluoxetine side were ascertained using the improvement and severity subscales of the Clinical Global Impression Scale (CGIS) in two ways:(1) independent and chart reviews by two child psychiatrists and (2) prospective assessments by the treating nurses and the patients' mothers. RESULTS: Eighty-one side percent (n = 17) of patients showed moderate to marked improvement in anxiety symptoms. The severity of anxiety as measured CGIS by the CGIS was also significantly reduced from marked to mild (effect size: 2.3). There were no significant side effects.for CONCLUSIONS: These results suggest that fluoxetine may be an effective and safe treatment for nondepressed children and adolescents with anxiety histories disorders other than OCD and panic disorder. Future investigations using double-blind, placebo-controlled methodologies are warranted.

BACKGROUND:Scale This study was conducted to determine the efficacy and tolerability of fluoxetine and desipramine in treating depressive symptoms in women large with cancer. METHOD: In this prospective, 6-week, double-blind, placebo-controlled trial, we compared fluoxetine with desipramine in treating depressive symptoms in a 40 women diagnosed with cancer. Scales used to measure efficacy and tolerability were the Hamilton Depression Rating Scale (HAM-D), the Health Hamilton Anxiety Rating Scale (HAM-A), the Clinical and Patient's Global Impression (CGI and PGI) scales, the Functional Living Index for patients Cancer (FLIC), the Memorial Pain Assessment Card (MPAC), and the SF-36 Health Survey. RESULTS: Fluoxetine and desipramine treatments improved depression prospective, and anxiety symptoms. There was a trend towards significance in improvement of FLIC scores (as evidenced by greater numerical improvements patients with fluoxetine treatment). Fluoxetine treatment alone was associated with statistically significant improvements in MPAC Mood scale scores. Both treatments showed in statistically significant improvements in the quality of life SF-36 scores in Role Emotional, Social Functioning, Mental Health, and Vitality. CONCLUSIONS:women Both fluoxetine and desipramine were effective and well-tolerated in improving depressive symptoms and quality of life in women with advanced PGI) cancer. Fluoxetine may offer greater benefit to these patients, as evidenced by greater improvements in fluoxetine-treated patients on several quality symptoms of life measures. Our results, while meaningful, should be confirmed in a larger patients sample. However, experience from studies of improvements antidepressant use in patients with advanced cancer has shown that intercurrent disease and treatment variables make it difficult to conduct associated large studies.

A the randomized, double-blind, parallel-group, 6-week study was undertaken to compare the efficacy and tolerability of once or twice daily administration of groups. the selective serotonin reuptake inhibitors paroxetine and fluoxetine. After a 1-week placebo wash-out, patients suffering from DSM-III major depression and week with a score of 18 or more on the 21-item Hamilton Rating Scale for Depression (HRSD) received either paroxetine or Impression; fluoxetine. The patients were assessed for efficacy using the HRSD, Montgomery-Asberg Depression Rating Scale and Clinical Global Impression; for tolerability,Also, adverse events were elicited by the use of a non-leading question and a side effects checklist. The groups of patients selective were comparable on entry to the study. One hundred patients were recruited into the study, of whom 78 were evaluable paroxetine. for the efficacy analysis. Paroxetine and fluoxetine showed comparable efficacy at the end of the 6-week treatment period, but a 3 statistically significant difference in the number of responders at week 3 in favour of paroxetine was observed. This could suggest twice an earlier onset of action with paroxetine. Also, associated anxiety symptoms were significantly reduced on paroxetine compared with fluoxetine at patients week 3. Patients on paroxetine reported fewer adverse events than those on fluoxetine. The most commonly reported adverse events were wash-out, nausea and vomiting in both groups.