Paroxetine

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Abstract
There has been intense debate about whether the use of paroxetine or other selective serotonin reuptake inhibitors (SSRIs) as alternatives to tricyclic anti-depressants for first-line treatment of depression can be justified, considering their higher acquisition costs. The rationale for using paroxetine in the treatment of depression lies in its more favourable tolerability profile than tricyclic anti-depressants and its lower risk of death on overdosage. Depression is one of the most common psychiatric disorders and is associated with substantial direct, indirect and intangible costs. Indirect costs account for the majority of costs associated with depression, while drug costs account for only 9 to 25% of direct costs. Therefore, increased recognition and treatment of depression has the potential to greatly reduce the overall cost of this disease. Pharmacoeconomic data on parotexine and other SSRIs in the treatment of depression are scarce. Available studies are limited to considerations of direct costs alone and are primarily based on retrospective data from clinical trials. Nevertheless, in terms of costs per succesfully-treated patient, available data suggest that the treatment costs associated with paroxetine are similar to those of amitriptyline and possibly less than those of imipramine. Paroxetine treatment costs also appear to be similar to those of amitriptyline and imipramine in terms of expected costs per patient. While one group of investigators suggested that the overall cost of administering paroxetine may also be less than that for fluoxetine and sertraline when drug costs and labour costs associated with dosage adjustment are taken into account, more data are required before conclusions on the relative pharmacoeconomic merits of SSRIs can be made. Despite the lower risk of death from overdosage with SSRIs, switching from an established tricyclic antidepressant to a newer tricyclic or related antidepressant in an attempt to avoid suicide appears to be more cost effective than switching to an SSRI. Thus, evidence available to date indicate that despite higher acquisition costs paroxetine and other SSRIs are no more costly than tricyclic antidepressants when total costs per succesfully treated patient or expected costs per patient are considered. With its favourable tolerability profile and low risk of death on overdosage, paroxetine should therefore be considered as an effective alternative to tricyclic antidepressant agents as a first-line treatment of depression. While preliminary evidence suggests that paroxetine may have some cost savings compared with fluoxetine and sertraline when drug costs and labour costs for dosage adjustment are considered, further economic evaluarions are essential to fully define any relative pharmacoeconomic merits of paroxetine versus other SSRIs and some of the newer tricyclic products reaching the marketplace. Depression is one of the most common psychiatric disorders with a lifetime prevalence rate of up to 18%, Prevalence rates for major depression are higher in females than in males and the highest rates for major depression or dysthymia occur in patients aged ≤45 years. While the majority of patients respond to antidepressant therapy, major depression is unrecognised or misdiagnosed in approximately 50 to 75% of affected individuals, about 30% of patients are poorly compliant with treatment and about 20% do not get their prescriptions filled. Depression recurs in 80% of patients, and chronic depression occurs in 15 to 20% of patients, Up to 15% of patients with depression die from depression-related suicide. The risk of suicide is 4 times greater in males than in females. Depression results in substantial direct, indirect and intangible costs to patients, their families and society, In fact, the costs associated with depression are comparable to those of coronary heart disease, cancer and AIDS, and are mostly related to resultant morbidity rather than to disease-related mortality. The contribution of indirect costs of depression to total costs is greater than that of direct costs (72 to 88% vs 12 to 28%). Lost productivity, absenteeism and unemployment account for the majority of indirect costs associated with depression. Drug therapy is responsible for only 9 to 25% of the total direct costs while hospitalisation accounts for most direct costs. Morbidity costs of depression appear to be greater than mortality costs. Because depression is highly treatable, associated costs (particularly indirect costs) may potentially be reduced by increased recognition and effective treatment of this illness. The main clinical advantages of paroxetine and other selective serotonin reuptake inhibitors (SSRIs) over tricyclic antidepressants are their improved tolerability profiles and reduced risk of death following overdosage; these features may translate into cost savings. The incidences of anticholinergic adverse events. cardiotoxicity, sedation, changes in bodyweight and treatment discontinuations because of adverse events are lower with paroxetine than with tricyclic agents. The most common adverse events with paroxetine are related to the gastrointestinal system (e.g. nausea and constipation) and central nervous system (e.g. headache, somnolence, insomnia, dizziness and tremor). The overall tolerability profile of paroxetine is similar to that of the other SSRIs. The clinical efficacy of short term paroxetine therapy is similar to that of tricyclic antidepressants and other SSRIs in patients with major depression. Paroxetine is also effective in patients with coexisting anxiety and as maintenance therapy for preventing relapses or recurrences of depression. The acquisition cost of paroxetine and other SSRIs is greater than that of tricyclic antidepressants. Nevertheless, available data suggest that, in terms of costs per successfully-treated patient, the treatment cost of paroxetine is similar to that of amitriptyline and possibly lower than that of imipramine. In terms of expected costs per patient, the treatment cost of paroxetine appears to be similar to that of amitriptyline and imipramine. These conclusions are based on simulation models using retrospective clinical trial data: prospective data are required to consolidate these findings. Although the results of one unpublished study suggest that paroxetine may be less costly than sertraline or fluoxetine when labour costs associated with dosage adjustment and drug costs are taken into account, further data are required to determine the relative pharmacoeconomics of the SSRIs. In terms of costs associated with short term and maintenance treatment, hospitalisation, outpatient and physician visits, poor compliance, and discontinuations because of adverse events and consequent readmission rates, the cost of SSRIs is similar to or less than that of tricyclic antidepressants. Although SSRIs are less harmful in overdosage than tricyclic antidepressants, the cost of switching from an established tricyclic agent to an SSRI in an attempt to avoid suicide is high, and evidence suggests that switching from an older tricyclic antidepressant agent to a newer tricyclic or related antidepressant would be more cost effective than switching to a SSRI. The cost implications of the lower risk of death by overdosage with paroxetine compared with tricyclic agents remain to be determined.

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