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Biomedical subjects

S A Montgomery

Publications and source records attributed to S A Montgomery.

At least 19 recordsLinked to original sources
PubMed2005

Antidepressants and seizures: emphasis on newer agents and clinical implications.

Seizures are a known, relatively rare, consequence of antidepressant treatment. Risk estimates vary depending on the study, source of data and patient population, predisposed vs. nonpredisposed. For newer antidepressants (e.g. selective serotonin reuptake inhibitors, bupropion, mirtazepine, etc.), the risk is generally considered to be low (0.0%-0.4%) and not very different from the incidence of first seizure in the general population (0.07%-0.09%). Risk with tricyclic antidepressants at effective therapeutic doses is relatively high (0.4% to 1-2%). Seizure following overdose is a significant and relatively frequent event for some antidepressants. Patients being considered for antidepressant treatment should be screened for predisposition to seizures. Predisposed patients should receive antidepressants cautiously. The seizure potential of antidepressants in patients without a predisposition is low, especially for newer antidepressants. Seizure risk, along with other drug-related considerations, e.g. weight gain, sexual dysfunction and sedation, should be considered when prescribing an antidepressant.

Adrenergic Uptake Inhibitors↗
PubMed2004

Absence of discontinuation symptoms with agomelatine and occurrence of discontinuation symptoms with paroxetine: a randomized, double-blind, placebo-controlled discontinuation study.

The effects of an abrupt interruption of agomelatine, a new melatonergic/serotonergic antidepressant, were explored in a double-blind, placebo-controlled study. Paroxetine was used as active control. After 12 weeks of double-blind treatment with agomelatine 25 mg/day or paroxetine 20 mg/day, sustained remitted depressed patients were randomized for 2 weeks, under double-blind conditions, to placebo or to their initial antidepressant treatment. Discontinuation symptoms were assessed at the end of the first and second week of discontinuation with the Discontinuation Emergent Signs and Symptoms (DESS) checklist. One hundred and ninety-two sustained remitted patients were randomized to the 2-week discontinuation period. Patients who discontinued agomelatine did not experience more discontinuation symptoms than those who continued on agomelatine. Patients who discontinued paroxetine for placebo experienced significantly more DESS discontinuation symptoms, during the first week, compared to those who continued with paroxetine (respective mean number of emergent symptoms: 7.3+/-7.1 and 3.5+/-4.1, P<0.001). No significant difference was shown between the continuing and interrupting groups in the second week of discontinuation. By contrast to paroxetine, abrupt cessation of agomelatine is not associated with discontinuation symptoms.

Acetamides↗
PubMed2004

A randomised study comparing escitalopram with venlafaxine XR in primary care patients with major depressive disorder.

This 8-week, randomised, double-blind study compared the efficacy and tolerability of escitalopram to that of venlafaxine XR in primary care patients with major depressive disorder. The efficacy of escitalopram (10- 20 mg; n = 148) was similar to venlafaxine XR (75- 150 mg; n = 145), based on mean change from baseline to week 8 in Montgomery and Asberg Depression Rating Scale total score. In ad hoc analyses, escitalopram-treated patients achieved sustained remission significantly faster than did venlafaxine-treated patients. More venlafaxine-treated patients had nausea, constipation, and increased sweating (p < 0.05). When treatment was completed after 8 weeks, significantly more venlafaxine-treated patients had discontinuation symptoms (p < 0.01). Thus escitalopram treatment was similar to venlafaxine treatment with respect to efficacy and was better tolerated by patients in primary care.

Adult↗
PubMed2002

Antidepressant medications: a review of the evidence for drug-induced sexual dysfunction.

BACKGROUND: Sexual dysfunction is recognised as a potential side effect of antidepressant therapy. However, there is little detailed information on the prevalence of drug-induced sexual dysfunction or the differences, if any, between available drugs. This article is a critical review of the literature in the area. METHODS: English-language studies on sexual dysfunction and depression or antidepressant treatments were identified by searching Medline and supplemented by manual review of their reference lists and recent journal issues available in a library. Trials of antidepressant use in anxiety disorders were identified from a Medline search and their adverse events tables scanned for data on sexual dysfunction. All trials were assessed according to predefined criteria. RESULTS: Sexual dysfunction is widespread in the healthy non-depressed population and is a recognised symptom of depression and/or anxiety disorders. Sexual dysfunction has been reported with all classes of antidepressants (MAOIs, TCAs, SSRIs, SNRIs and newer antidepressants) in patients with depression and various anxiety disorders. Numerous studies have been published, but only one used a validated sexual function rating scale and most lacked either a baseline or a placebo control or both. None met all of the pre-defined assessment criteria. LIMITATIONS: The search techniques may have missed some studies and publication bias cannot be ruled out. CONCLUSIONS: The existing literature confirms sexual dysfunction as a possible adverse event of all antidepressants, but it is not sufficiently robust to support claims for differences in the incidence of drug-induced sexual dysfunctions between existing antidepressant therapies. Prescribing decisions should be based on a careful assessment of the benefits and risks of therapy in the individual patient.

Adult↗
PubMed2002

Moclobemide is effective and well tolerated in the long-term pharmacotherapy of social anxiety disorder with or without comorbid anxiety disorder.

Social phobia (social anxiety disorder) is a highly prevalent and chronic disorder that is associated with significant comorbidity and disability. Despite recent advances in the pharmacotherapy of the disorder, there is a paucity of randomized controlled trials on patients with comorbid disorders and on maintenance treatment. A randomized placebo-controlled, double-blind multi-site trial of moclobemide, a reversible inhibitor of monoamine oxidase A, was undertaken with 390 subjects. After an initial 12 weeks, there was the option of continuing for an additional 6 months of treatment. The primary efficacy parameter chosen was responder status as defined by the Clinical Global Impression scale change item. From week 4 onwards, there was a significantly higher response rate on moclobemide than on placebo. Superiority of medication over placebo was similar in patients with comorbid anxiety disorders (33% of subjects) and without, as well as in patients with different subtypes of social anxiety disorder; indeed, treatment with moclobemide rather than placebo was the strongest predictor of response. Adverse events were similar across treatment groups, and were typically mild and transient. In the extension phase, response rates remained higher in the moclobemide group, and ratings of tolerability were equally high in both groups. Thus, in a large sample of social anxiety disorder patients with and without comorbid anxiety disorders, moclobemide was both effective and well-tolerated in the short as well as long-term. These data confirm and extend previous findings on the value of moclobemide in the treatment of social anxiety disorder, and strengthen the range of therapeutic options for managing this important disorder.

Adolescent↗
PubMed2001

Escitalopram (S-enantiomer of citalopram): clinical efficacy and onset of action predicted from a rat model.

Escitalopram is the active S-enantiomer of citalopram. In a chronic mild stress model of depression in rats, treatments with both escitalopram and citalopram were effective; however, a faster time to onset of efficacy compared to vehicle treatment was observed for escitalopram-treated (5 mg/kg/day) than for citalopram-treated (10 mg/kg/day) rats at Week 1. To study the predictability of this observation in the clinic, we analysed 4-week data from an 8-week, double-blind, randomised, placebo-controlled, flexible-dose study that compared escitalopram and citalopram to placebo in primary care patients with major depressive disorder (baseline Montgomery and Asberg Depression Rating Scale (MADRS) scores > or =22 and < or =40). Since the flexible dosing started after Week 4, analysis of 4-week data ensured that the patients received fixed doses of 10 mg/day escitalopram (155 patients), 20 mg/day citalopram (160 patients), or placebo (154 patients). The efficacy analysis showed a significantly superior therapeutic effect for escitalopram versus placebo from Week 1 onwards (observed cases) with an adjusted mean change in MADRS at Week 4 (last observation carried forward) of 2.7 points (P=0.002). By comparison, 20 mg/day citalopram did not demonstrate a statistically significant effect compared to placebo. Escitalopram was well tolerated with an adverse event profile similar to that of citalopram. The preclinical observation that escitalopram possesses a faster time to onset of efficacy than citalopram was also seen in primary care patients with major depressive disorder. Thus, escitalopram is efficacious in depression and the effect occurs earlier than for citalopram.

Animals↗
PubMed2001

Citalopram 20 mg, 40 mg and 60 mg are all effective and well tolerated compared with placebo in obsessive-compulsive disorder.

Serotonin reuptake inhibitors appear to be uniquely effective treatments for obsessive-compulsive disorder (OCD). This double-blind, placebo-controlled study was the first trial to assess the efficacy of the most selective of the serotonin reuptake inhibitors, citalopram, in OCD. A total of 401 patients were randomized to receive citalopram 20, 40 or 60 mg/day or placebo for 12 weeks. All three doses of citalopram were significantly more effective than placebo measured on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) change score (P < 0.01). The highest response rate, defined as 25% improvement in Y-BOCS entry score, was observed in the 60 mg group (65%). This compared with 52% and 57.4% in the 40 mg and 20 mg groups. Response rate on placebo was 36.6% (P < 0.05 for all three doses of citalopram compared to placebo). There was no significant difference between the individual doses of citalopram. An advantage was seen for citalopram on the Sheehan Disability Scale compared with placebo (P < 0.05 on all three citalopram groups versus placebo for both the work situation and the family life and home responsibilities and P < 0.05 on citalopram 60 mg and 20 mg versus placebo for the social life and home activities). Citalopram was well tolerated; only 4 to 6 patients in each dose group discontinued the study prematurely due to adverse events.

Activities of Daily Living↗
PubMed2001

A meta-analysis of the efficacy and tolerability of paroxetine versus tricyclic antidepressants in the treatment of major depression.

This meta-analysis examined efficacy and tolerability data from 39 randomized, double-blind, parallel-group studies comparing paroxetine (n = 1924) with clomipramine (n = 141) or other tricyclic antidepressants (TCAs; n = 1693) in the treatment of major depression. Paroxetine had comparable antidepressant efficacy to TCAs, including clomipramine, as assessed by response rates based on a < or = 50% reduction in Hamilton Rating Scale for Depression (HAMD) total score (58-66%) and a HAMD total score < or = 8 (38-48%) at endpoint, and absolute improvements in HAMD total score (mean change 12.3-14.5). Absolute improvements in HAMD anxiety factor scores were similar between paroxetine and clomipramine (mean change 2.3 versus 2.4, P = 0.566), but paroxetine was statistically significantly more effective on this measure than other TCAs (mean change 2.3 versus 2.1, P = 0.028). The proportion of patients who experienced adverse events with > 1% incidence was statistically significantly lower with paroxetine than with clomipramine (64% versus 77%, P = 0.02) or other TCAs (64% versus 71%, P < 0.001). The incidence of patient withdrawals due to adverse events was also statistically significantly lower with paroxetine than with clomipramine (17% versus 27%, P = 0.014), but an advantage seen for paroxetine over other TCAs (17% versus 20%, P = 0.130) did not reach statistical significance. These findings demonstrate that paroxetine has comparable efficacy to and better tolerability than TCAs, including clomipramine, and is therefore an appropriate treatment strategy for depression, particularly in the common clinical situation where concomitant anxiety symptoms are present.

Antidepressive Agents, Tricyclic↗
PubMed2001

Predictors of response to pharmacotherapy with citalopram in obsessive-compulsive disorder.

Although serotonin reuptake inhibitors (SRIs) are the medications of choice in the treatment of obsessive-compulsive disorder (OCD), only 50-60% of patients respond to a single trial of any of these agents. Improved knowledge of the predictors of response to treatment may have important clinical implications. Data from a large randomized placebo-controlled trial of citalopram in OCD was analysed using logistic regression to determine predictors of response. Demographic (age, sex), clinical (OCD severity and duration, depression severity, prior treatment) and trial variables (citalopram dose, treatment duration) were included. Subjects with longer duration of OCD, more severe OCD symptoms or previous selective SRI use were less likely to be responders in the citalopram trial. In contrast, subjects who received adequate medication doses for sufficient periods of time in the citalopram trial were more likely to be responders. Despite greater awareness of OCD in recent years, there is evidence that the disorder continues to be underdiagnosed and undertreated. The data here emphasize the crucial importance of early diagnosis and treatment of OCD, and of pharmacotherapy with appropriate dose and duration.

Adolescent↗
PubMed2000

Pharmacotherapy of depression and mixed states in bipolar disorder.

The treatment of bipolar depression requires the resolution of depression and the establishment of mood stability. A basic problem is that the treatments used in treating bipolar depression were developed and proven effective for other disease states: antidepressants for unipolar depression, and mood stabilizers for mania. The panel addressed four unresolved questions regarding depression in relation to bipolar disorder: (1) the relative effectiveness of different antidepressant treatments; (2) the relative likelihood of mood destabilization with different antidepressant treatments; (3) the effectiveness and role of mood-stabilizing medicines as antidepressants; and (4) the optimal approach to mixed states. The selection of an antidepressant depends both on its relative lack of mania- or hypomania-provoking potential and on its effectiveness against bipolar depression. There is little definitive evidence distinguishing effectiveness of the major groups of antidepressive agents, so side-effect profiles and pharmacokinetics are major considerations. The underlying bipolar disorder should be treated with mood stabilizers started simultaneously with any antidepressive treatments. Lithium, divalproex sodium and carbamazepine have all been found to be helpful, to some extent, in treating bipolar depressive episodes as well as for long-term mood stabilization. There is little evidence for long-term benefits of antidepressive agents in bipolar disorder, and some evidence that they may destabilize the disorder. Therefore, in contrast to the long-term use of mood-stabilizers, antidepressant use is recommended on a temporary basis. The duration of antidepressant treatment is determined by past history in terms of liability for mood destabilization, and by the ability of the patient to tolerate gradual antidepressant discontinuation without return of depression. Mixed states, where symptoms of depression and mania coexist, are regarded as a predictor of relatively poor response to lithium, and divalproex has been found to be more effective. Carbamazepine may too be useful in mixed states. Most patients with mixed states in actual practice require combinations of mood stabilizers, though there is little controlled data regarding such co-prescription, especially from a long-term perspective.

Antidepressive Agents↗
PubMed2000

Social phobia: diagnosis and epidemiology, neurobiology and pharmacology, comorbidity and treatment.

Social phobia is a common disorder associated with significant psychosocial impairment, representing a substantial public health problem largely determined by the high prevalence, and the lifelong chronicity. Social phobia starts in early childhood or adolescence and is often comorbid with depression, other anxiety disorders, alcohol and substance abuse or eating disorders. This cascade of comorbidity, usually secondary to social phobia, increases the disability associated with the condition. The possibility that social phobia may be a trigger for later developing comorbid disorders directs attention to the need for early effective treatment as a preventive measure. The most recent drug class to be investigated for the psychopharmacological treatment of social phobia is the SSRI group for which there is growing support. The other drug classes that have been evaluated are monoamine oxidase inhibitors (MAOIs), benzodiazepines, and beta-blockers. The SSRIs represent a new and attractive therapeutic choice for patients with generalized social phobia. Recently the first, large scale, placebo-controlled study to assess the efficacy of drug treatment in generalized social phobia has been completed with paroxetine. Paroxetine was more effective in reducing the symptoms than placebo and was well tolerated. Many now regard SSRIs as the drugs of choice in social phobia because of their effectiveness and because they avoid the problems of treatment with benzodiazepines or classical MAOIs.

Adrenergic beta-Antagonists↗
PubMed2000

Disabilities and quality of life in pure and comorbid generalized anxiety disorder and major depression in a national survey.

Using a nationally representative sample, this study examines the disease-specific impairments of DSM-IV generalized anxiety disorder (GAD) by comparing them to the impairments associated with major depressive disorder (MDD). Results are based on 4181 respondents between the ages of 18-65 years who were interviewed with the 12-month version of the Munich-Composite International Diagnostic Interview as part of the German National Health Interview and Examination Survey-Mental Health Supplement (GHS). After controlling for age, gender, and other psychopathology, 'pure' current GAD without MDD (n = 33), pure MDD (n = 344) and comorbid GAD and MDD (n = 40) were each associated with high impairment as defined by poor self-perceived health, at least 3 days limited or impaired in the past month, and low quality of life scores [from the Short Form-36 Health Survey (SF-36)]. Quality of life scores on several of the SF-36 scales were significantly lower for respondents with pure GAD as compared to respondents with pure MDD. Overall, the results show that DSM-IV GAD is associated with high impairment even after controlling for other psychopathology. The impairment outcomes for GAD were comparable in size to those for MDD. These findings underline the significance of this disorder from a clinical and social perspective and provide support for the independent diagnostic status of GAD.

Adolescent↗