Long-term treatment of psychotic (delusional) depression with fluvoxamine: an open pilot study

The aim of this open pilot study was to evaluate the efficacy of fluvoxamine in the continuation as well as in the maintenance therapy of delusional depression. Thirty patients with recurrent, unipolar depression (DSM-IV criteria) were selected who had at least one depressive episode during the 18 months preceding the delusional depressive index episode and were treated with fluvoxamine 300 mg/day. Twenty-five of them had a sustained response to this short-term treatment and agreed to enter into the 30-month follow up study. All participants completed the follow up period. No relapse was observed during the 6 months of continuation therapy. During the further 24 months of maintenance therapy, 80% of the patients remained well, whereas 20% (five out of 25) had a single recurrence. Based on these observations, fluvoxamine might be a promising drug for long-term therapy of delusional depression. Further controlled studies are required to confirm this finding.     

Social adjustment and the course of affective illness: a one-year controlled longitudinal study involving bipolar and unipolar outpatients

The association between social adjustment and recurrent affective episodes was examined in 27 recovered bipolar patients and 24 recovered unipolar patients who had been receiving maintenance treatment for at least 1 year. Social adjustment variables and psychiatric status were assessed by bimonthly interviews over the 1-year period using the Social Adjustment Scale (SAS) and the Research Diagnostic Criteria (RDC). Variations in the social adjustment scores were analyzed in the 2 months preceding the onset of a recurrent affective episode. Furthermore, social adjustment variables at entry into the study were assessed to investigate whether there was any association between these and the potential timing of a recurrent episode. Results revealed no significant deterioration in social adjustment during the 2 months preceding a recurrent affective episode. However, it was demonstrated that there was a relationship between a patient's overall social adjustment score at entry into the study and the onset of recurrent affective episodes, independent of any residual depressive symptomatology. Specifically, impaired work adjustment in bipolar and unipolar patients was associated with recurrent episodes. Impaired social and leisure activities adjustment in bipolar patients was also associated with recurrent episodes, and impaired marital adjustment in unipolar patients was associated with recurrent episodes. These results suggest that social maladjustment could be a risk factor for both unipolar and bipolar recurrent affective episodes and that impairment in specific areas of social functioning could be used to predict outcome.     

The prevalence of verbal communication disability in patients with Parkinson''s disease

BACKGROUND: We evaluated and compared the efficacy and safety of sertraline and fluvoxamine in a randomized, double-blind, parallel-group study during a follow-up of 24 months. METHOD: Sixty-four patients with recurrent, unipolar depression (DSM-IV criteria) who had at least one depressive episode during the 18 months preceding the index episode were accepted into the trial. Patients were randomly assigned to one of the two long-term treatment groups and evaluated monthly by trained psychiatrists, blinded to treatment option, on the basis of the Hamilton Rating Scale for Depression. RESULTS: All patients completed the 24-month follow-up period. Sertraline and fluvoxamine showed an equal efficacy in preventing new recurrences. In fact, there was no significant difference in survival rates between the two medication groups: 7 sertraline-treated patients (21.9%) and 6 fluvoxamine-treated patients (18.7%) had a single new recurrence (z = 0.14; p = .88). Moreover, recurrence observed during maintenance therapies was less severe and/or of shorter duration than index episodes. CONCLUSION: Long-term treatment with sertraline or fluvoxamine has been shown to be effective for prevention of highly recurrent unipolar depression. The high tolerability of these compounds, together with their prophylactic effectiveness, has an important role in improving the quality of life of these patients.     

Effect of arginine vasopressin (AVP) inhibitor in the inhibition of the peritumoral edema

BACKGROUND: Major depressive disorder is often marked by repeated episodes of depression. We describe recovery from major depression across multiple mood episodes in patients with unipolar major depression at intake and examine the association of sociodemographic and clinical variables with duration of illness. METHODS: A cohort of 258 subjects treated for unipolar major depressive disorder was followed up prospectively for 10 years as part of the Collaborative Depression Study, a multicenter naturalistic study of the mood disorders. Diagnoses were made according to the Research Diagnostic Criteria, and the course of illness was assessed with the Longitudinal Interval Follow-up Evaluation. Survival analyses were used to calculate the duration of illness for the first 5 recurrent mood episodes after recovery from the index episode. RESULTS: Diagnosis remained unipolar major depressive disorder for 235 subjects (91%). The median duration of illness was 22 weeks for the first recurrent mood episode, 20 weeks for the second, 21 weeks for the third, and 19 weeks for the fourth and fifth recurrent mood episodes; the 95% confidence intervals were highly consistent. From one episode to the next, the proportion of subjects who recovered by any one time point was similar. For subjects with 2 or more recoveries, the consistency of duration of illness from one recovery to the next was low to moderate. None of the sociodemographic or clinical variables consistently predicted duration of illness. CONCLUSION: In this sample of patients treated at tertiary care centers for major depressive disorder, the duration of recurrent mood episodes was relatively uniform and averaged approximately 20 weeks.     

Buspirone augmentation of antidepressant therapy

Thirty outpatients meeting DSM-III-R or DSM-IV criteria for major depression, single or recurrent episode, and failing to respond to an adequate trial of an antidepressant (>6 weeks at recommended dosage) received buspirone (20-30 mg/day) for 4 or 5 weeks in addition to their existing antidepressant. Of the 22 patients who had buspirone added to their selective serotonin reuptake inhibitor antidepressant regimen (fluoxetine, paroxetine, or citalopram), 59% (13/22) showed complete or partial remission of their depressive symptomatology. Similarly, 63% (5/8) of patients treated with buspirone in addition to clomipramine showed complete or partial remission. The mean score on the Clinical Global Impressions Scale fell by 64% (from 4.7 to 1.7; p < 0.0001) in treatment responders (complete and partial). No serious side effects were observed during combination therapy. Seventy-nine percent (11/14) of initial responders (both complete and partial) who remained on augmentation therapy for at least 4 months were symptom-free at follow-up. Buspirone augmentation may produce marked clinical improvement in depressed patients who are initially unresponsive to standard antidepressant therapy.     

Suicide mortality in patients on lithium maintenance therapy

Mood disorders are frequently recurrent and it has been shown that maintenance treatment can reduce long-term morbidity in this condition. It has also been shown that mood disorders carry an increased risk of suicide and that a significant proportion of individuals who commit suicide suffer from a mood disorder. This paper reports the results of a long term follow-up of a cohort of patients attending a specialist mood disorder clinic over a period of 18 years. Sixty-seven suffered from unipolar depression and 36 had bipolar or schizo-affective disorders In order to qualify for entry to the cohort the unipolar patients had to have had at least three episodes of depression and those with bipolar disorders had to have had at least three episodes - with at least one manic episode and one depressive episode. All patients were treated with lithium. The initial treatment refusal rate and drop our rates were low. The mortality from suicide in this group was compared with that reported in five recent studies - all of which involved patients who had not been given maintenance therapy. The standardised mortality ratio (SMR) for all causes for the whole group was 0.93. There were two suicides. In one case the patient had continued treatment with lithium until death and in the other the patient had discontinued treatment 12 months before death. The overall suicide rate was 1.3 per 1000 patient years. Amongst similar groups of patients who had not been given maintenance therapy suicide rates of about 5.5 per 1000 patient years have been reported. It is concluded that maintenance treatment of mood disorders reduces the suicide rate in this vulnerable group of patients.     

Comparison of once-daily doses of omeprazole (40 and 20 mg) and placebo in the treatment of benign gastric ulcer: a multicenter, randomized, double-blind study

OBJECTIVE: The purpose of this multicenter, randomized, double-blind study, conducted in 520 patients, was to compare the efficacy and safety of omeprazole (40 and 20 mg once daily) with placebo in the treatment of benign gastric ulcer. METHODS: Treatment with omeprazole or placebo lasted 4 wk; those whose ulcers remained unhealed continued the same treatment regimen for an additional 4 wk. The effects of therapy were determined by endoscopy and assessment of GI symptoms. Safety and tolerability were evaluated through reported adverse events, physical examinations, and laboratory tests. RESULTS: At weeks 4 and 8, the proportion of patients with healed ulcers was significantly greater in the omeprazole 40- and 20-mg groups than in the placebo group (p < 0.01). At week 8, the healing rate was significantly greater in the 40-mg group than in the 20-mg group (82.7 vs 74.8%, p < 0.05). In patients with large ulcers (>1 cm), the 40-mg regimen was associated with a significantly higher healing rate (78.9%) than both the 20-mg regimen (61.4%) and placebo (34.6%) at week 8 (p < 0.05 vs omeprazole 20 mg; p < 0.01 vs placebo). Healing rates in patients with small ulcers were similar for the 40- and 20-mg groups. Omeprazole was well tolerated, with no significant differences versus placebo in the overall incidence of clinical or laboratory adverse events. CONCLUSIONS: Omeprazole 40 and 20 mg, administered once daily, healed a significantly greater proportion of patients than did placebo. The 40-mg regimen offered significant advantages over the 20-mg regimen in patients with large ulcers.     

A 26-year-old man with shoulder pain

The acute effects of flumazenil, a benzodiazepine (BZD) receptor antagonist in long-term BZD users were used as a possible test to detect physiological dependence. Thirty-four subjects (20 females, 14 males) aged 26-48 years (mean + SD, 42.4+/-8.5 years), all chronic users of low doses of diazepam (5-20 mg/day, 14.2+/-4.8 mg/day) for 5 to 28 years (10.5+/-6 years), received a single 1-mg i.v. flumazenil dose or saline, infused slowly under double-blind conditions. Physiological dependence was suggested as all patients receiving flumazenil developed an anxiety reaction while the placebo group did not. Flumazenil triggered a qualitatively different reaction amounting to a panic attack during infusion in nine out of 15 patients. These patients had a diagnosis of panic disorder or a history of panic attacks. Caution should be exercised when giving flumazenil to panic patients who are taking BZDs as maintenance treatment.     

A prospective 12-year study of subsyndromal and syndromal depressive symptoms in unipolar major depressive disorders

BACKGROUND: Investigations of unipolar major depressive disorder (MDD) have focused primarily on major depressive episode remission/recovery and relapse/recurrence. This is the first prospective, naturalistic, long-term study of the weekly symptomatic course of MDD. METHODS: The weekly depressive symptoms of 431 patients with MDD seeking treatment at 5 academic centers were divided into 4 levels of severity: (1) depressive symptoms at the threshold for MDD; (2) depressive symptoms at the threshold for minor depressive or dysthymic disorder (MinD); (3) subsyndromal or subthreshold depressive symptoms (SSDs), below the thresholds for MinD and MDD; and (4) no depressive symptoms. The percentage of weeks at each level, number of changes in symptom level, and medication status were analyzed overall and for 3 subgroups defined by mood disorder history. RESULTS: Patients were symptomatically ill in 59% of weeks. Symptom levels changed frequently (1.8/y), and 9 of 10 patients spent weeks at 3 or 4 different levels during follow-up. The MinD (27%) and SSD (17%) symptom levels were more common than the MDD (15%) symptom level. Patients with double depression and recurrent depression had more chronic symptoms than patients with their first lifetime major depressive episode (72% and 65%, respectively, vs 46% of follow-up weeks). CONCLUSION: The long-term weekly course of unipolar MDD is dominated by prolonged symptomatic chronicity. Combined MinD and SSD level symptoms were about 3 times more common (43%) than MDD level symptoms (15%). The symptomatic course is dynamic and changeable, and MDD, MinD, and SSD symptom levels commonly alternate over time in the same patients as a symptomatic continuum of illness activity of a single clinical disease.     

Major depressive disorder: a prospective study of residual subthreshold depressive symptoms as predictor of rapid relapse

BACKGROUND: The study tested whether level of recovery from major depressive episodes (MDEs) predicts duration of recovery in unipolar major depressive disorder (MDD) patients. METHODS: MDD patients seeking treatment at five academic centers were followed naturalistically for 10 years or longer. Patients were divided on the basis of intake MDE recovery into residual depressive symptoms (SSD; N=82) and asymptomatic (N=155) recovery groups. They were compared on time to first episode relapse/recurrence, antidepressant medication, and comorbid mental disorders. Recovery level was also compared to prior history of recurrent MDEs ( > 4 lifetime episodes) as a predictor of relapse/recurrence. RESULTS: Residual SSD compared to asymptomatic recovery patients relapsed to their next MDE > 3 times faster (median=68 vs. 23 weeks) and to any depressive episode > 5 times faster (median=33 vs. 184 weeks). Residual SSD recovery status was significantly associated with early episode relapse (OR=3.65) and was stronger than history of recurrent MDEs (OR=1.64). Rapid relapse in the SSD group could not be attributed to higher comorbidity or lower antidepressant treatment. LIMITATIONS: Although inter-rater agreement on weekly depressive symptom ratings was very high (ICC > 0.88), some error may exist in assigning recovery levels. Antidepressant treatments were recorded, but were not controlled. CONCLUSIONS: MDE recovery is a powerful predictor of time to episode relapse/recurrence. Residual SSD recovery is associated with very rapid episode relapse which supports the idea that SSD is an active state of illness. Asymptomatic recovery is associated with prolonged delay in episode recurrence. These findings of this present study have important implications for the goals of treatment of MDD and for defining true MDE recovery.     

Radiotherapy and concurrent chemotherapy for the treatment of locally advanced head and neck squamous cell carcinoma

PURPOSE: To determine whether combination 5-fluorouracil, cisplatin, and interferon alfa, an active regimen in advanced esophageal cancer, is efficacious as induction therapy before esophagectomy. MATERIALS AND METHODS: Forty-four patients with potentially resectable esophageal/gastroesophageal junction adenocarcinoma or squamous cell carcinoma were entered into a phase I/II study of this chemotherapeutic regimen and concurrent external-beam radiotherapy before resection. The initial 16 patients were treated with prolonged-infusion 5-fluorouracil (300 mg/m2 on days 1 to 28), cisplatin (20 mg/m2 on days 1 to 5 and 24 to 28), interferon alfa (3 x 10(6) U/m2 intravenously on days 1 to 5 and 24 to 28; subcutaneous injection every other day on days 6 to 23), and radiation (4000 cGy). The subsequent 28 patients were treated over 21 days with two modifications: dose escalation of 5-fluorouracil (250 to 350 mg/m2) and double-fractionated radiotherapy to a total dose of 4500 cGy. RESULTS: Forty-one patients completed chemoradiotherapy and were evaluable for toxicity. Adverse events were substantial but tolerable, and most toxic episodes were hematologic and gastrointestinal. Three patients died, and one patient had progressive disease before resection. Of the 37 patients eligible for curative resection, 36 had all gross tumor removed. Thirty-three (80%) patients had a major pathologic response: 10 (24%) with no residual tumor and 23 with only microscopic residual tumor. Median survival for all patients was 27 months and for responders was 36 months. CONCLUSIONS: This combination regimen is active but yields results similar to those of other chemoradiotherapy phase II trials; therefore, the contribution of interferon alfa to treatment efficacy remains uncertain. The true worth of preoperative chemoradiotherapy is unknown pending results of phase III trials.     

Complex patterns of immediate early gene induction in rat brain following brightness discrimination training and pseudotraining

Data presented during the 1996 CINP President's Workshop supported the conclusion that unipolar major depressive disorder (MDD) is a pleomorphic mood disorder consisting of a cluster of depressive subtypes existing in a relatively homogeneous symptomatic clinical continuum, extending from subsyndromal depressive symptomatology (SSD) through minor depressive episode, dysthymic disorder, major depressive episode and double depression. This indicates that common unipolar depressive subtypes can be conceptualized as alternate forms or different symptomatic phases of the same parent illness. Although there appears to be great overlap across time in the symptomatological expressions of these clinical depressive subtypes, they may be derived from different etiological and genetic factors. The one exception may be major depressive episode with psychotic features, which exists on a severity continuum with other subtypes of unipolar MDD, but does not appear to be on a symptomatic continuum with dysthymic, subsyndromal or minor depressions. By contrast, SSD and minor depressive disorder represent clinically significant depressive subtypes, which are commonly observed during the course of illness of patients with unipolar major depressive illness. Compared to no depressive symptoms, SSD is associated with harmful dysfunction, as evidenced by significant increases in psychosocial impairment, signifying that SSD is an active, inter-episode disease state of unipolar major depressive disorder. Finally, SSD, possibly jointly with subthreshold anxiety symptoms, may also represent potent risk factors for rapid depressive episode relapse. In the aggregate, these findings and conclusions have broad and important implications for diagnostic and treatment strategies of unipolar MDD.     

With reference to: RAYS 21,3,1996 venous thromboembolism

This study evaluated paroxetine as a possible treatment for premature ejaculation. Sixty two patients affected by primary premature ejaculation were randomly assigned to two groups. A and B, and treated with two different treatment schedules. Patients assigned to group A were treated with paroxetine 20 mg p.o. daily for six months; patients assigned to group B were treated with paroxetine 20 mg p.o. daily for fourteen days, and than dose was reduced to 10 mg for a total treatment period of six months. Only one patient reported significative side effects (weakness). Positive clinical results were obtained, at the end of the treatment, in 89 per cent of group A and 88 per cent of group B. In patients with primary premature ejaculation, paroxetine represents, in our opinion, the best therapeutic option for its efficacy and lack of significant side effects.     

Propofol decreases ocular pressure in outpatients undergoing trabeculectomy

OBJECTIVES: The present study was conducted to compare pharmacokinetic behaviors of nicardipine enantiomers given in different doses with different formulations of racemic nicardipine in healthy volunteers. METHODS: One or two 20-mg racemic nicardipine tablets, and a 40-mg sustained-release capsule of nicardipine were administered to eight healthy volunteers in a crossover fashion and pharmacokinetic parameters were evaluated. Enantiomer concentrations were determined by GC-MS combined with chiral stationary phase HPLC. RESULTS AND CONCLUSIONS: Serum concentration of (+)-nicardipine was approximately 2-3 times higher than that of (-)-nicardipine in 20- and 40-mg doses of conventional formulations and a non-linear increase in bioavailability with dose was demonstrated. The value for AUC of (+)-nicardipine was approximately 2.3-2.8 times greater than that of the (-)-nicardipine (P < 0.05) when 20 and 40 mg racemic nicardipine were administered in a conventional preparation. Relative bioavailability of the sustained-release preparation vs the conventional preparation was 28% and 44% for (+)- and (-)-nicardipine, respectively, for the 40-mg dose.     

Hypothalamic-pituitary-adrenal axis activity in depressive illness. Its relationship to classification

Serum cortisol response to the 1-mg overnight dexamethasone suppression test was studied in 221 depressed patients and 109 nondepressed psychiatric controls. Nonsuppression distinguished patients with primary unipolar depression (65/146) from patients with secondary unipolar depression (0/42) and nondepressed controls (0/109). Furthermore, nonsuppression distinguished the three familial subtypes of primary unipolar depressive illness: familial pure depressive disease (FPDD; 38/50 patients), sporadic depressive disease (SDD; 24/55 patients), and depression spectrum disease (3/41 patients). Moderate elevations in baseline serum cortisol levels were found in FPDD, SDD, and bipolar depression. Medication did not affect the results. The data suggest that the depressive syndrome is composed of separate illnesses, each of which has a distinctive pattern of hypothalamic-pituitary-adrenal axis activity during the depressed state as well as a specific clinical and familial psychiatric history.     

Treatment of postoperative nausea and vomiting with single intravenous doses of dolasetron mesylate: a multicenter trial. Dolasetron Mesylate PONV Treatment Study Group

This study was conducted to determine the efficacy and safety of four intravenous (I.V.) doses of dolasetron, an investigational 5-HT3 receptor antagonist, for the treatment of postoperative nausea and/or vomiting (PONV) after outpatient surgery under general anesthesia. This multicenter, randomized, double-blind trial compared the antiemetic efficacy of 12.5, 25, 50, or 100 mg I.V. dolasetron with placebo over 24 h using complete response (no emetic episodes and no rescue medication), time to first emetic episode or rescue medication, and patient nausea and satisfaction with antiemetic therapy as rated by visual analog scale (VAS). Of 1557 patients enrolled, 620 patients were eligible for treatment. Complete response rates for all dolasetron doses--12.5 mg (35%), 25 mg (28%), 50 mg (29%), and 100 mg (29%)--were significantly more effective than placebo (11%, P < 0.05). There was a significant gender interaction for complete response (P < 0.01). Of the patients in the 25-mg and 100-mg dose groups, 12% and 13%, respectively, experienced no nausea (VAS score < 5 mm) versus 5% in the placebo group (P < 0.05). There were no clinically relevant changes in vital signs or laboratory values and no trends with dose for adverse events. Dolasetron is effective for treating PONV and has an adverse event profile similar to that of placebo. The 12.5-mg dose was as effective as larger doses for complete response. IMPLICATIONS: Nausea and vomiting are common problems for postsurgical patients. In this study of 620 patients undergoing surgery, a 12.5-mg dose of intravenous dolasetron, a new serotonin-receptor blocker, was significantly more effective than placebo in treating established postoperative nausea and vomiting. Dolasetron 12.5 mg was as safe as placebo.     

Selective activation of postsynaptic 5-HT1A receptors induces rapid antidepressant response

It has been reported that the 5-HT1A autoreceptor antagonist pindolol can accelerate the antidepressant response to the selective serotonin (5-HT) reuptake inhibitor (SSRI) paroxetine, presumably by preventing the initial decrease in firing activity of 5-HT neurons produced by the SSRI. The present study was aimed at further exploring this treatment strategy in three groups of 10 patients with unipolar major depression allocated sequentially to three treatment arms for 28 days. The administration of the selective 5-HT1A agonist buspirone (20 mg/day for 1 week and 30 mg/day thereafter) with pindolol (2.5 mg TID) was used to activate selectively postsynaptic 5-HT1A receptors. This combination produced a greater than 50% reduction of depressive symptoms in the first week in 8 of 10 patients and the response was sustained for the remainder of the trial. In contrast, the combination of tricyclic antidepressant drugs devoid of effect on the 5-HT reuptake process (desipramine or trimipramine, 75 mg/day for 1 week and 150 mg/day thereafter) with pindolol resulted in only one of ten patients achieving a 50% improvement after 28 days. The combination of the SSRI fluvoxamine (50 mg/day for 1 week and 100 mg/day thereafter) with pindolol produced a marked antidepressant effect but did not act as rapidly as the buspirone plus pindolol combination with none, four, and eight patients achieving a 50% amelioration after 7, 14, and 21 days of treatment, respectively. These results provide further evidence that pindolol may accelerate the antidepressant effect of drugs that alter the function of the 5-HT neurons and that the selective activation of postsynaptic 5-HT1A receptors may induce a rapid and robust antidepressant response.     

Do patients with chronic pain selectively attend to pain-related information?: preliminary evidence for the mediating role of fear

To date, there appears to be no consensus of opinion as to whether the adrenal glands are hyperresponsive during depression and, if so, whether this a state-dependent phenomenon. We aimed to determine the effects of antidepressant treatment on ACTH-induced cortisol responses in patients with melancholic depression. Seven female patients with DSM-III-R major depressive disorder, non-psychotic, melancholic subtype, were evaluated using the following rating scales: the Hamilton Depression Rating Scale, the Montgomery-Asberg Depression Rating Scale and the Newcastle Endogenicity Scale. All subjects were then given an intravenous bolus dose (250 micrograms) of tetracosactrin, a potent stimulus of adrenocortical hormone secretion. Plasma levels of cortisol were measured at times 0, + 30, + 60, + 90, + 120 and + 180 min. Patients were then randomised to receive either 50 mg of sertraline or 20 mg of paroxetine (both of which are selective serotonin re-uptake inhibitors) and were re-tested while medication-free. Treatment resulted in a significant decrease in delta (the difference between the baseline values and the maximum increase post-ACTH administration) cortisol values of 1633.3 +/- 378.5 nmol/l vs. 595.1 +/- 207.7 nmol/l. Successful pharmacological treatment of major depressive disorder appears to be associated with a reduction in ACTH-induced cortisol release in drug-free patients.     

Nicotine patch and paroxetine for smoking cessation.

Smokers (N?=?224) were randomized to 1 of 3 groups: (a) transdermal system (TNS) + placebo; (b) TNS + paroxetine (20 mg); (c) TNS + paroxetine (40 mg). Assignment to treatment was double-blind. Nicotine patch (TNS) treatment was provided for 8 weeks; paroxetine or placebo was provided for 9 weeks. Abstinence rates at Weeks 4, 10, and 26 were as follows: (a) TNS + placebo: 45%, 36%, and 25%; (b) TNS + paroxetine (20 mg): 48%, 33%, and 21 %; (c) TNS + paroxetine (40 mg): 57%, 39%, and 27%. The differences were not statistically significant. The combined treatment was more effective in reducing both craving and depression symptoms associated with smoking cessation. A subgroup analysis comparing compliant participants was also conducted. Abstinence rates at Weeks 4, 10, and 26 were as follows: (a) TNS + placebo: 46%, 35%, and 24%; (b) TNS + paroxetine (20 mg): 64%, 43%, and 33%; (c) TNS + paroxetine (40 mg): 74%, 51%, and 38%. The differences between paroxetine groups and placebo at Week 4 were statistically significant. Although paroxetine may add value to the current standard of care in excess of potential risk, more conclusive evidence is needed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Treatment of febrile seizures with intermittent clobazam

Fifty children, 24 female and 26 male, with ages varying from 6 to 72 months (mean = 23.7 m.) that experienced at least one febrile seizure (FS) entered a prospective study of intermittent therapy with clobazam. Cases with severe neurological abnormalities, progressive neurological disease, afebrile seizures, symptomatic seizures of other nature, or seizures during a central nervous system infection were excluded. Seizures were of the simple type in 25 patients, complex in 20 and unclassified in 5. The mean follow-up period was 7.9 months (range = 1 to 23 m.), and the age at the first seizure varied from 5 to 42 months (mean = 16.8 m.). Clobazam was administered orally during the febrile episode according to the child's weight: up to 5 kg, 5 mg/day; from 5 to 10 kg, 10 mg/day; from 11 to 15 kg, 15 mg/day, and over 15 kg, 20 mg/day. There were 219 febrile episodes, with temperature above 37.8 degrees C, in 40 children during the study period. Twelve children never received clobazam and 28 received the drug at least once. Drug efficacy was measured by comparing FS recurrence in the febrile episodes that were treated with clobazam with those in which only antipyretic measures were taken. Ten children (20%) experienced a FS during the study period. Of the 171 febrile episodes treated with clobazam there were only 3 recurrences (1.7%), while of the 48 episodes treated only with antipyretic measures there were 11 recurrences (22.9%), a difference highly significant (p < 0.0001). Adverse effects occurred in 10/28 patients (35.7%), consisting mainly in vomiting, somnolence and hyperactivity. Only one patient had recurrent vomiting which lead to drug interruption. These effects did not necessarily occurred in every instance the drug was administered, being present in one febrile episode and not in the others. We conclude that clonazepam is safe and efficacious in preventing FS recurrence. It may be an alternative to diazepam in the intermittent treatment of FS recurrence.