Selective Serotonin Reuptake Inhibitors

The Parkinson's-Reversing Breakthrough

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Results from uncontrolled studies suggest that SSRIs are effective for anxiety in PD (42-44). In an open-label study (n = 10), Menza et al. (42) reported that citalopram (mean dose 19mg/d) improved anxiety in depressed PD patients. In a study of 30 patients, paroxetine (20 mg twice daily) reduced psychic and somatic anxiety symptoms, as well as depressive symptoms after six weeks (43). Sertraline was also found to have anxiolytic effects in PD patients (44). Although these data are derived from uncontrolled studies, many specialists prefer to use SSRIs for managing anxiety and depression in PD (49).

The SSRIs are relatively well tolerated, although acute, treatment-emergent side effects such as agitation, diarrhea/loose stools, insomnia, nausea, and sedation may occur. Occasionally, SSRIs may worsen tremor, and chronic use is associated with an increased risk of developing endocrinologic and metabolic adverse effects, such as hyponatremia, sexual dysfunction, and weight gain (Table 1) (50-52). The concomitant use of amantadine has been reported to reduce the risk of SSRI-induced sexual dysfunction (53). Reversible SSRI-induced worsening of parkinsonism has also been reported, but data are conflicting regarding the magnitude of this risk (54-56). Pharmacodynamic studies have not detected any significant reduction of motor function in patients with PD treated with SSRIs (57-58). Patients on a concomitant monoamine oxidase-B (MAO-B) inhibitor (e.g., rasagiline, selegiline) may be at increased risk of developing 5-HT syndrome; however, the overall risk appears to be minimal. In one survey-based study, the frequency of 5-HT syndrome in patients on concomitant selegiline was 0.24%, with 0.04% of patients experiencing serious symptoms (59). Data for the safety of SSRIs in combination with rasagiline are limited. In a study of rasagiline in PD, among those taking SSRIs (n = 77), there

TABLE 1 Comparison of Selected Antidepressant Side Effects

Sexual

Sedation Antimuscarinic Hypotension Weight gain dysfunction

TCAs

TABLE 1 Comparison of Selected Antidepressant Side Effects

TCAs

Amitriptyline

+++

+++

++

+++

+

Doxepin

++

+++

++

++

+

Imipramine

++

++

+++

++

+

Desipramine

+

+

+

+

0

Nortriptyline

+

+

+

+

0

SSRIs

Citalopram

+

+

0

+

++

Escitalopram

+

+

0

+

++

Fluoxetine

0

0

0

+

+++

Fluvoxamine

0

0

0

++

++

Paroxetine

+

+

0

++

+++

Sertraline

0

0

0

+

++

Other

Bupropion

0

+

0

0

0

Duloxetine

+

++

0

0

++

Mirtazapine

++a

+

++

+++a

++

Nefazodone

++

0

++

0

+

Venlafaxine

+

+

0

+

Abbreviations: +, minor; ++, moderate; +++, major; 0, nonsignificant; SSRIs, selective serotonin reuptake inhibitors; TCAs, tricyclic antidepressants. Source: From Refs. 50-52.

aAt low doses.

Abbreviations: +, minor; ++, moderate; +++, major; 0, nonsignificant; SSRIs, selective serotonin reuptake inhibitors; TCAs, tricyclic antidepressants. Source: From Refs. 50-52.

were no significant differences in adverse events with rasagiline compared to placebo (60). Abrupt discontinuation of SSRIs after extended treatment may precipitate a withdrawal or discontinuation syndrome, characterized by somatic and psychological symptoms that resemble anxiety (61). Therefore, if discontinuation is required, a gradual tapering of the dosage is recommended, particularly with short half-life agents such as paroxetine.

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