Paroxetine: an update of its use in psychiatric disorders in adults

Paroxetine is a selective serotonin reuptake inhibitor (SSRI), with antidepressant and anxiolytic activity. In 6- to 24-week well designed trials, oral paroxetine 10 to 50 mg/day was significantly more effective than placebo, at least as effective as tricyclic antidepressants (TCAs) and as effective as other SSRIs and other antidepressants in the treatment of major depressive disorder. Relapse or recurrence over 1 year after the initial response was significantly lower with paroxetine 10 to 50 mg/day than with placebo and similar to that with imipramine 50 to 275 mg/day. The efficacy of paroxetine 10 to 40 mg/day was similar to that of TCAs and fluoxetine 20 to 60 mg/day in 6- to 12-week trials in patients aged > or =60 years with major depression. Paroxetine 10 to 40 mg/day improved depressive symptoms to an extent similar to that of TCAs in patients with comorbid illness, and was more effective than placebo in the treatment of dysthymia and minor depression. Paroxetine 20 to 60 mg/day was more effective than placebo after 8 to 12 weeks' treatment of obsessive-compulsive disorder (OCD), panic disorder, social anxiety disorder (social phobia), generalised anxiety disorder (GAD) and post-traumatic stress disorder (PTSD). Improvement was maintained or relapse was prevented for 24 weeks to 1 year in patients with OCD, panic disorder, social anxiety disorder or GAD. The efficacy of paroxetine was similar to that of other SSRIs in patients with OCD and panic disorder and similar to that of imipramine but greater than that of 2'chlordesmethyldiazepam in patients with GAD. Paroxetine is generally well tolerated in adults, elderly individuals and patients with comorbid illness, with a tolerability profile similar to that of other SSRIs. The most common adverse events with paroxetine were nausea, sexual dysfunction, somnolence, asthenia, headache, constipation, dizziness, sweating, tremor and decreased appetite. In conclusion, paroxetine, in common with other SSRIs, is generally better tolerated than TCAs and is a first-line treatment option for major depressive disorder, dysthymia or minor depression. Like other SSRIs, paroxetine is also an appropriate first-line therapy for OCD, panic disorder, social anxiety disorder, GAD and PTSD. Notably, paroxetine is the only SSRI currently approved for the treatment of social anxiety disorder and GAD, which makes it the only drug of its class indicated for all five anxiety disorders in addition to major depressive disorder. Thus, given the high degree of psychiatric comorbidity of depression and anxiety, paroxetine is an important first-line option for the treatment of major depressive disorder, OCD, panic disorder, social anxiety disorder, GAD and PTSD.     

Spotlight on paroxetine in psychiatric disorders in adults

Paroxetine is a selective serotonin reuptake inhibitor (SSRI), with antidepressant and anxiolytic activity. In 6- to 24-week well designed trials, oral paroxetine 10 to 50 mg/day was significantly more effective than placebo, at least as effective as tricyclic antidepressants (TCAs) and as effective as other SSRIs and other antidepressants in the treatment of major depressive disorder. Relapse or recurrence over 1 year after the initial response was significantly lower with paroxetine 10 to 50 mg/day than with placebo and similar to that with imipramine 50 to 275 mg/day. The efficacy of paroxetine 10 to 40 mg/day was similar to that of TCAs and fluoxetine 20 to 60 mg/day in 6- to 12-week trials in patients aged > or = 60 years with major depression. Paroxetine 10 to 40 mg/day improved depressive symptoms to an extent similar to that of TCAs in patients with comorbid illness, and was more effective than placebo in the treatment of dysthymia and minor depression. Paroxetine 20 to 60 mg/day was more effective than placebo after 8 to 12 weeks' treatment of obsessive-compulsive disorder (OCD), panic disorder, social anxiety disorder (social phobia), generalised anxiety disorder (GAD) and post-traumatic stress disorder (PTSD). Improvement was maintained or relapse was prevented for 24 weeks to 1 year in patients with OCD, panic disorder, social anxiety disorder or GAD. The efficacy of paroxetine was similar to that of other SSRIs in patients with OCD and panic disorder and similar to that of imipramine but greater than that of 2'chlordesmethyldiazepam in patients with GAD. Paroxetine is generally well tolerated in adults, elderly individuals and patients with comorbid illness, with a tolerability profile similar to that of other SSRIs. The most common adverse events with paroxetine were nausea, sexual dysfunction, somnolence, asthenia, headache, constipation, dizziness, sweating, tremor and decreased appetite. In conclusion, paroxetine, in common with other SSRIs, is generally better tolerated than TCAs and is a first-line treatment option for major depressive disorder, dysthymia or minor depression. Like other SSRIs, paroxetine is also an appropriate first-line therapy for OCD, panic disorder, social anxiety disorder, GAD and PTSD. Notably, paroxetine is the only SSRI currently approved for the treatment of social anxiety disorder and GAD, which makes it the only drug of its class indicated for all five anxiety disorders in addition to major depressive disorder. Thus, given the high degree of psychiatric comorbidity of depression and anxiety, paroxetine is an important first-line option for the treatment of major depressive disorder, OCD, panic disorder, social anxiety disorder, GAD and PTSD.     

Paroxetine: safety and tolerability issues

Paroxetine is a selective serotonin re-uptake inhibitor (SSRI) available in immediate release and controlled release (CR) formulations. Paroxetine is the most potent inhibitor of serotonin re-uptake among the now available SSRIs. Paroxetine has been approved for the treatment of major depressive disorder (MDD), obsessive–compulsive disorder, panic disorder (PD), generalised anxiety disorder, post traumatic stress disorder (PTSD), and social anxiety disorder (SAD) in adults, whereas paroxetine CR is approved for the treatment of MDD, SAD, PD and premenstrual dysphoric disorder in adults. The overall efficacy of paroxetine seems to be comparable to other SSRIs in the treatment of approved indications, although paroxetine treatment induces more sedation, constipation, sexual dysfunction, discontinuation syndrome and weight gain than other SSRIs. Recent data suggest that paroxetine treatment leads to increased rates of congenital malformations, although this evidence is not conclusive. Paroxetine and paroxetine CR are not indicated for use in the paediatric population and are categorised as Pregnancy Class D. In conclusion, whether the tolerability profile of paroxetine differs substantially from other new antidepressants (including other SSRIs) needs to be determined in adequately powered well-designed randomised controlled comparative clinical trials.     

Paroxetine: safety and tolerability issues

Paroxetine is a selective serotonin re-uptake inhibitor (SSRI) available in immediate release and controlled release (CR) formulations. Paroxetine is the most potent inhibitor of serotonin re-uptake among the now available SSRIs. Paroxetine has been approved for the treatment of major depressive disorder (MDD), obsessive-compulsive disorder, panic disorder (PD), generalised anxiety disorder, post traumatic stress disorder (PTSD), and social anxiety disorder (SAD) in adults, whereas paroxetine CR is approved for the treatment of MDD, SAD, PD and premenstrual dysphoric disorder in adults. The overall efficacy of paroxetine seems to be comparable to other SSRIs in the treatment of approved indications, although paroxetine treatment induces more sedation, constipation, sexual dysfunction, discontinuation syndrome and weight gain than other SSRIs. Recent data suggest that paroxetine treatment leads to increased rates of congenital malformations, although this evidence is not conclusive. Paroxetine and paroxetine CR are not indicated for use in the paediatric population and are categorised as Pregnancy Class D. In conclusion, whether the tolerability profile of paroxetine differs substantially from other new antidepressants (including other SSRIs) needs to be determined in adequately powered well-designed randomised controlled comparative clinical trials.     

Efficacy and tolerability of controlled-release paroxetine

Paroxetine controlled-release (CR) was developed with the objective of minimizing the occurrence and severity of selective serotonin reuptake inhibitor (SSRI)-associated adverse events, thereby improving clinical outcomes. Paroxetine CR delays the onset and controls the rate of absorption of medication. Multicenter controlled clinical trials have found lower rates of early-onset, treatment-associated nausea and lower dropout rates from adverse events in depressed patients treated with paroxetine CR compared with those treated with the conventional, immediate-release formulation. At the same time, clinical response and remission rates are favorable. Other studies have demonstrated the efficacy and tolerability of paroxetine CR in geriatric depression, panic disorder, and social anxiety disorder. The CR formulation of paroxetine appears to represent an effective pharmacokinetic approach to minimizing SSRI adverse events and thereby enhancing clinical outcomes.     

Clinical experience with paroxetine in social anxiety disorder

Paroxetine is a selective serotonin reuptake inhibitor (SSRI) with proven efficacy in the treatment of depression, panic disorder and obsessive-compulsive disorder. Evidence that paroxetine may be effective in social anxiety disorder (social phobia) first arose from open-label studies. More recently, three multicentre, randomized, placebo-controlled trials have been performed, each lasting 12 weeks, to assess the efficacy and tolerability of paroxetine in the treatment of social anxiety disorder, and these studies are reviewed here. The data from all three studies consistently demonstrated that paroxetine was effective in reducing both the symptoms of anxiety and the disability and impairment of social anxiety disorder. Paroxetine performed significantly better than placebo on all primary (Liebowitz Social Anxiety Scale, Clinical Global Impression) and secondary (Social Avoidance and Distress Scale, Sheehan Disability Scale) outcome measures. Adverse events were restricted to those already known to be associated with SSRIs, no serious adverse events associated with medication were experienced, and the numbers withdrawing from the studies were not significantly different in the paroxetine and control groups. Taken together, these studies confirm that paroxetine is an effective and well tolerated treatment for patients with social anxiety disorder.     

An evaluation of paroxetine in generalised social anxiety disorder

It is estimated that social anxiety disorder affects approximately 13.3% individuals within the community at some point in their lifetime and is associated with significant functional impairment. A variety of drug groups have demonstrated efficacy in treating social anxiety disorder, including selective serotonin reuptake inhibitors (SSRIs). Paroxetine is an SSRI approved by the FDA and Health Canada for the treatment of a variety of psychiatric conditions. Paroxetine has been the most studied agent in social anxiety disorder and has been shown to be effective in short-term, fixed- and flexible-dose placebo-controlled trials, as well as in long-term treatment. The pharmacotherapy of social phobia will be reviewed, with a special focus on investigations with paroxetine.     

Paroxetine treatment of major depressive disorder

Major depression is recognized as a common, often chronic and recurrent illness that is associated with significant disability and comorbidity. The treatment of patients with major depressive disorder has advanced tremendously in the past decade as a result of the availability of effective and well-tolerated antidepressants. Paroxetine is a widely studied selective serotonin reuptake inhibitor (SSRI) with evidence for efficacy and safety that is supported by a large body of published literature. Evidence for the efficacy and tolerability of anew controlled-release formulation of paroxetine also has been published. Findings from paroxetine clinical studies have added considerably to our knowledge and understanding of the treatment of major depressive disorder, particularly with regard to duration of treatment, the need for treating to full remission and with full doses, and treatment of patients with concurrent symptoms of anxiety.     

Luteal phase administration of agents for the treatment of premenstrual dysphoric disorder

This review focuses on current information about luteal phase administration (i.e. typically for the last 2 weeks of the menstrual cycle) of pharmacological agents for the treatment of premenstrual dysphoric disorder (PMDD). Compared with continuous administration, a luteal phase administration regimen reduces the exposure to medication and lowers the costs of treatment. Based on evidence from randomised clinical trials, SSRIs are the first-line treatment for PMDD at this time. Of these agents, sertraline, fluoxetine and paroxetine (as an extended-release formulation) are approved by the US FDA for luteal phase, as well as continuous, administration. Clinical trials of these agents and citalopram have demonstrated that symptom reduction is similar with both administration regimens. When used to treat PMDD, SSRI doses are consistent with those used for major depressive disorder. The medications are well tolerated; discontinuation symptoms with this intermittent administration regimen have not been reported. Other medications that have been examined in clinical trials for PMDD or severe premenstrual syndrome (PMS) using luteal phase administration include buspirone, alprazolam, tryptophan and progesterone. Buspirone and alprazolam show only modest efficacy in PMS (in some but not all studies), but there may be a lower incidence of sexual adverse effects with these medications than with SSRIs. Symptom reduction with tryptophan was significantly greater than with placebo, but the availability of this medication is strictly limited because of safety concerns. Progesterone has consistently failed to show efficacy for severe PMS/PMDD in large, randomised, placebo-controlled trials.     

Advances in recognition and treatment of social anxiety disorder: a 10-year retrospective

Social anxiety disorder frequently begins in early life and is associated with the subsequent development of comorbid conditions such as depressive and substance use disorders. Social anxiety disorder, particularly the generalized subtype, is characterized by marked impairment in numerous functional domains, including education and social relations. Paroxetine, the first medication to receive an indication in the United States for the treatment of social anxiety disorder, has been shown to be effective in 50% to 60% of patients. The mechanism of action of paroxetine in the treatment of social anxiety disorder is at present unclear. A possible role for early treatment to prevent complications of social anxiety disorder should be explored.     

The selective serotonin reuptake inhibitor paroxetine is effective in more generalized and in less generalized social anxiety disorder

RATIONALE: The DSM-IV includes the specifier "generalized" to refer to social anxiety disorder (social phobia) patients if the fears include "most social situations". The focus on interventions such as the selective serotonin reuptake inhibitors (SSRIs) for generalized social anxiety disorder arguably runs the risk that inadequate treatment will be provided to patients with the non-generalized or discrete subtypes. There are, however, few data to address whether more generalized and less generalized subgroups of social anxiety disorder differ in response to medication. OBJECTIVE: To compare response of more generalized and less generalized social anxiety disorder to pharmacotherapy. METHODS: Data from three randomized placebo-controlled double-blind multicenter trials of the SSRI paroxetine in social anxiety disorder were pooled. Response on the Clinical Global Impression Global Improvement item was analyzed using logistic regression, and change in total Liebowitz Social Anxiety Score was analyzed using analysis of variance, with both models incorporating treatment (paroxetine vs placebo), subgroup (more generalized vs less generalized), demographic, and clinical variables. RESULTS: The prevalence of more generalized social anxiety disorder was higher in females than in males. However, there was no significant difference in terms of age or clinical characteristics (duration of condition, baseline pulse, mean arterial blood pressure). At treatment endpoint there were significant treatment effects (for paroxetine vs placebo), but no significant subgroup effects (for more generalized vs less generalized). CONCLUSIONS: Although the current database is limited insofar as few patients with discrete social anxiety disorder would have been included, it is helpful in addressing the value of medication for patients lying on the spectrum from generalized to non-generalized and discrete social anxiety disorder. Paroxetine was effective in both more generalized and in less generalized social anxiety disorder.     

Symptom-onset treatment for women with premenstrual dysphoric disorder

Symptoms of premenstrual dysphoric disorder (PMDD) respond to serotonin reuptake inhibitors when treatment is limited to 14 days of the menstrual cycle. Many women have less than a week of symptoms, and shorter treatment intervals would further reduce medication exposure and costs. METHODS: Twenty women with PMDD were randomly assigned to either paroxetine CR or placebo for 1 cycle and crossed over to the other condition for a second cycle. Subjects initiated treatment when premenstrual symptoms began and stopped within 3 days of beginning menses. RESULTS: Women took capsules for an average of 9 days (range, 3-15 days), including the first few days of menses. Moderate "PMDD level" symptoms occurred in 1 subject (6%) for 2 days and 4 subjects (24%) for 1 day before starting paroxetine or placebo. Daily Record of Severity of Problems scores were lower in the paroxetine group compared with the placebo group, although the differences were not statistically significant. However, the mean on-treatment Inventory of Depressive Symptomatology (clinician-rated) score for the paroxetine group was 17.9 +/- 8.3 compared with 31.5 +/- 11.2 in the placebo group (adjusted mean difference = 13.6, P = 0.009). Response (Clinical Global Impressions Scale score of 1 or 2) occurred in 70% of subjects randomized to paroxetine CR and 10% of those assigned to placebo (chi2(1) = 7.5, P = 0.006). Discontinuation symptoms did not differ in the groups. CONCLUSION: These data suggest the need to further evaluate symptom-onset treatment in a larger randomized clinical trial.     

Safety of benzodiazepines in the geriatric population

Generalised anxiety disorder (GAD) significantly impacts upon quality of life and has a chronic and persistent nature. GAD requires pharmacological therapies that are well-tolerated, lessen the mitigating effects of common comorbidities and do not pose a high risk for dependency or abuse. Selective serotonin and serotonin–noradrenaline re-uptake inhibitors have become more viable treatments for GAD than the traditionally used benzodiazepines due to greater efficacy and a more tolerable adverse event profile. Among these newer-generation antidepressants, only paroxetine and venlafaxine are currently FDA-approved for the treatment of GAD. Paroxetine was approved after three double-blind, placebo-controlled studies demonstrated its superior efficacy compared to placebo for short-term treatment of GAD. Venlafaxine was approved for both short- and long-term treatment of GAD after demonstrating efficacy in 8-week and 6-month double-blind, placebo-controlled trials. For both paroxetine and venlafaxine, the safety and tolerability profiles during treatment of GAD are consistent with those demonstrated during the short- and long-term treatment of patients with major depressive disorder.     

The safety of SSRIs in generalised anxiety disorder: any reason to be anxious?

Generalised anxiety disorder (GAD) significantly impacts upon quality of life and has a chronic and persistent nature. GAD requires pharmacological therapies that are well-tolerated, lessen the mitigating effects of common comorbidities and do not pose a high risk for dependency or abuse. Selective serotonin and serotonin-noradrenaline re-uptake inhibitors have become more viable treatments for GAD than the traditionally used benzodiazepines due to greater efficacy and a more tolerable adverse event profile. Among these newer-generation antidepressants, only paroxetine and venlafaxine are currently FDA-approved for the treatment of GAD. Paroxetine was approved after three double-blind, placebo-controlled studies demonstrated its superior efficacy compared to placebo for short-term treatment of GAD. Venlafaxine was approved for both short- and long-term treatment of GAD after demonstrating efficacy in 8-week and 6-month double-blind, placebo-controlled trials. For both paroxetine and venlafaxine, the safety and tolerability profiles during treatment of GAD are consistent with those demonstrated during the short- and long-term treatment of patients with major depressive disorder.     

Fluctuating serotonergic function in premenstrual dysphoric disorder and premenstrual syndrome: findings from neuroendocrine challenge tests

Rationale Premenstrual dysphoric disorder (PMDD) has been assumed to be a subtype of premenstrual syndrome (PMS) with depressive symptoms, such as depressive mood, tension, anxiety, and mood liability during luteal phase. At present, no conclusion has been established about serotonergic function in PMDD. Objective The purpose of this study was to investigate the serotonergic function of PMDD subjects in comparison to PMS without PMDD subjects and normal controls via neuroendocrine challenge tests. Subjects and methods Twenty-four women (seven with PMDD, eight with PMS without PMDD, and nine normal controls) were tested on three occasions (follicular phase, early luteal phase, and late luteal phase) receiving paroxetine 20 mg orally as a serotonergic probe at 8:00 a.m. Plasma ACTH and cortisol were measured prior to the administration and every hour for 6 h thereafter. Results As a whole, there were significant differences in serotonergic function measured by ACTH and cortisol responses to paroxetine challenge across these three groups. PMDD subjects showed higher serotonergic function in follicular phase but lower serotonergic function in luteal phase, compared with women with PMS without PMDD and normal controls. Conclusion The present findings suggest that PMDD women have fluctuating serotonergic function across their menstrual cycles and that the pattern may be different from PMS without PMDD.     

In vivo neuroimaging correlates of the efficacy of paroxetine in the treatment of mood and anxiety disorders

The advent of neuroimaging technology has brought with it a deeper understanding of brain function and structure in health and psychiatric illness. This article overviews pertinent findings from neuroimaging studies in mood and anxiety disorders. Paroxetine is a particularly well-studied psychopharmacologic agent in this regard. The findings of neuroimaging studies of paroxetine will be placed into perspective for a better understanding of the interaction of this selective serotonin reuptake inhibitor (SSRI) with the serotonergic and noradrenergic systems in the brain that mediate clinical efficacy. When considered in the context of a burgeoning literature on neuroimaging research of the pathophysiology of mood and anxiety disorders, the findings of paroxetine studies suggest a neurobiological explanation for the mechanisms whereby chronic administration of paroxetine affects neural systems involved in the pathophysiology of major depression and several anxiety disorders such as obsessive-compulsive disorder, posttraumatic stress disorder, and social anxiety disorder.     

Multicenter double blind study of paroxetine and amitriptyline in elderly depressed inpatients

Paroxetine is a phenylpiperidine compound which is a selective serotonin reuptake inhibitor (SSRI). Ninety-one hospitalised patients with a major depression (DSM-III) aged 65 and over from six Austrian and one German center were entered into the study, which compared the efficacy and tolerability of paroxetine versus amitriptyline. After 6 weeks both groups showed similarly good therapeutic results. In the paroxetine group, 64.3% of the patients had a 50% or more reduction of the HAMD total score compared to 58.1% in the amitriptyline group. Side effects were distributed similarly in both groups. Patients in the paroxetine group showed a higher incidence of anxiety and agitation; anticholinergic side effects were registered more often in the amitriptyline group.     

Paroxetine treatment of mood disorders in women: premenstrual dysphoric disorder and hot flashes

With the relatively recent introduction of the selective serotonin reuptake inhibitor (SSRI) class of antidepressants, increased attention has been focused on the use of antidepressants in the treatment of mood disorders across the female life cycle. Evidence for the efficacy of antidepressants in the treatment of premenstrual dysphoric disorder (PMDD) and hot flashes associated with menopause and breast cancer has emerged. The clinical trials experience with paroxetine and the controlled-release (CR) formulation of paroxetine is reviewed.     

Paroxetine: new indication. In social phobia: minimal assessment

Social phobia is generally defined as an intense and persistent fear of one or several social situations, with important repercussions for occupational activity or social life. Cognitive psychotherapy and antidepressants have partial efficacy. There is no reference drug therapy. In France, paroxetine is the first drug to be granted a licence for patients with social phobia. Clinical evaluation consists of data from four placebo-controlled trials lasting only 12 to 24 weeks. Treatment with paroxetine was associated with a significant improvement in standard social-phobia scores, although most patients remained symptomatic. Paroxetine is the best assessed selective serotonin reuptake inhibitor in this setting. However, long-term data are lacking, and the disorder is chronic. Paroxetine has not been compared with cognitive therapy. About one-third of patients in clinical trials stopped taking paroxetine, mainly because of adverse events. Gastrointestinal upset, sleep disturbance and ejaculatory problems are frequent. Paroxetine also has the potential to interact with other drugs. In practice, paroxetine may help some patients, provided they are aware of its limitations. The long-term effects of paroxetine in this setting remain unknown.     

Spotlight on sertraline in the management of major depressive disorder in elderly patients

Sertraline is a selective serotonin reuptake inhibitor (SSRI) with well established antidepressant and anxiolytic activity. Results from several well designed trials show that sertraline (50-200 mg/day) is effective in the treatment of major depressive disorder in elderly patients (> or =60 years of age). Primary endpoints in most studies included the Hamilton Depression Rating Scale (HDRS), Clinical Global Impression score and the Montgomery-Asberg Depression Rating Scale. Sertraline was significantly more effective than placebo and was as effective as fluoxetine, nortriptyline and imipramine in elderly patients. During one trial, amitriptyline was significantly more effective than sertraline (mean reduction from baseline on one of six primary outcomes [HDRS]), although no quantitative data were provided. Subgroup analysis of data from a randomised, double-blind trial in elderly patients with major depressive disorder suggests that vascular morbidity, diabetes mellitus or arthritis does not affect the antidepressant effect of sertraline. Secondary endpoints from these clinical trials suggest that sertraline has significant benefits over nortriptyline in terms of quality of life. In addition, significant differences favouring sertraline in comparison with nortriptyline and fluoxetine have been recorded for a number of cognitive functioning parameters. Sertraline is generally well tolerated in elderly patients with major depressive disorder and lacks the marked anticholinergic effects that characterise the adverse event profiles of tricyclic antidepressants (TCAs). The most frequently reported adverse events in patients aged > or =60 years with major depressive disorder receiving sertraline 50-150 mg/day were dry mouth, headache, diarrhoea, nausea, insomnia, somnolence, constipation, dizziness, sweating and taste abnormalities. The tolerability profile of sertraline is generally similar in younger and elderly patients. Sertraline has a low potential for drug interactions at the level of the cytochrome P450 enzyme system. In addition, no dosage adjustments are warranted for elderly patients solely based on age. CONCLUSION: Sertraline is an effective and well tolerated antidepressant for the treatment of major depressive disorder in patients aged > or =60 years. Since elderly patients are particularly prone to the anticholinergic effects of TCAs as a class, SSRIs such as sertraline are likely to be a better choice for the treatment of major depressive disorder in this age group. In addition, sertraline may have advantages over the SSRIs paroxetine, fluoxetine and fluvoxamine in elderly patients because of the drug's comparatively low potential for drug interactions, which is of importance in patient groups such as the elderly who are likely to receive more than one drug regimen.