Paroxetine (Page 13 of 17)

Dose Dependency of Adverse Events:

A comparison of adverse event rates in a fixed-dose study comparing 10, 20, 30, and 40 mg/day of paroxetine tablets with placebo in the treatment of major depressive disorder revealed a clear dose dependency for some of the more common adverse events associated with use of paroxetine tablets, as shown in Table 5:

Table 5 Treatment-Emergent Adverse Experience Incidence in a Dose-Comparison Trial in the Treatment of Major Depressive Disorder^*

* Rule for including adverse events in table: Incidence at least 5% for 1 of paroxetine groups and ≥ twice the placebo incidence for at least 1 paroxetine group.
Body System/Preferred Term	Placebo	Paroxetine Tablets
	n=51	10 mg n=102	20 mg n=104	30 mg n=101	40 mg n=102
Body As A Whole
Asthenia	0.0%	2.9%	10.6%	13.9%	12.7%
Dermatology
Sweating	2.0%	1.0%	6.7%	8.9%	11.8%
Gastrointestinal
Constipation	5.9%	4.9%	7.7%	9.9%	12.7%
Decreased Appetite	2.0%	2.0%	5.8%	4.0%	4.9%
Diarrhea	7.8%	9.8%	19.2%	7.9%	14.7%
Dry Mouth	2.0%	10.8%	18.3%	15.8%	20.6%
Nausea	13.7%	14.7%	26.9%	34.7%	36.3%
Nervous System
Anxiety	0.0%	2.0%	5.8%	5.9%	5.9%
Dizziness	3.9%	6.9%	6.7%	8.9%	12.7%
Nervousness	0.0%	5.9%	5.8%	4.0%	2.9%
Paresthesia	0.0%	2.9%	1.0%	5.0%	5.9%
Somnolence	7.8%	12.7%	18.3%	20.8%	21.6%
Tremor	0.0%	0.0%	7.7%	7.9%	14.7%
Special Senses
Blurred Vision	2.0%	2.9%	2.9%	2.0%	7.8%
Urogenital System
Abnormal Ejaculation	0.0%	5.8%	6.5%	10.6%	13.0%
Impotence	0.0%	1.9%	4.3%	6.4%	1.9%
Male Genital Disorders	0.0%	3.8%	8.7%	6.4%	3.7%

In a fixed-dose study comparing placebo and 20, 40, and 60 mg of paroxetine tablets in the treatment of OCD, there was no clear relationship between adverse events and the dose of paroxetine tablets to which patients were assigned. No new adverse events were observed in the group treated with 60 mg of paroxetine tablets compared to any of the other treatment groups.

In a fixed-dose study comparing placebo and 10, 20, and 40 mg of paroxetine tablets in the treatment of panic disorder, there was no clear relationship between adverse events and the dose of paroxetine tablets to which patients were assigned, except for asthenia, dry mouth, anxiety, libido decreased, tremor, and abnormal ejaculation. In flexible-dose studies, no new adverse events were observed in patients receiving 60 mg of paroxetine tablets compared to any of the other treatment groups.

In a fixed-dose study comparing placebo and 20, 40, and 60 mg of paroxetine tablets in the treatment of social anxiety disorder, for most of the adverse events, there was no clear relationship between adverse events and the dose of paroxetine tablets to which patients were assigned.

In a fixed-dose study comparing placebo and 20 and 40 mg of paroxetine tablets in the treatment of generalized anxiety disorder, for most of the adverse events, there was no clear relationship between adverse events and the dose of paroxetine tablets to which patients were assigned, except for the following adverse events: Asthenia, constipation, and abnormal ejaculation.

In a fixed-dose study comparing placebo and 20 and 40 mg of paroxetine tablets in the treatment of posttraumatic stress disorder, for most of the adverse events, there was no clear relationship between adverse events and the dose of paroxetine tablets to which patients were assigned, except for impotence and abnormal ejaculation.

Adaptation to Certain Adverse Events:

Over a 4- to 6-week period, there was evidence of adaptation to some adverse events with continued therapy (e.g., nausea and dizziness), but less to other effects (e.g., dry mouth, somnolence, and asthenia).

Male and Female Sexual Dysfunction with SSRIs:

Although changes in sexual desire, sexual performance, and sexual satisfaction often occur as manifestations of a psychiatric disorder, they may also be a consequence of pharmacologic treatment. In particular, some evidence suggests that selective serotonin reuptake inhibitors (SSRIs) can cause such untoward sexual experiences.

Reliable estimates of the incidence and severity of untoward experiences involving sexual desire, performance, and satisfaction are difficult to obtain, however, in part because patients and physicians may be reluctant to discuss them. Accordingly, estimates of the incidence of untoward sexual experience and performance cited in product labeling are likely to underestimate their actual incidence.

In placebo-controlled clinical trials involving more than 3,200 patients, the ranges for the reported incidence of sexual side effects in males and females with major depressive disorder, OCD, panic disorder, social anxiety disorder, GAD and PTSD are displayed in Table 6.

Table 6 Incidence of Sexual Adverse Events in Controlled Clinical Trials

	Paroxetine Tablets	Placebo
n (males)	1446	1042
Decreased Libido	6-15%	0-5%
Ejaculatory Disturbance	13-28%	0-2%
Impotence	2-9%	0-3%
n (females)	1822	1340
Decreased Libido	0-9%	0-2%
Orgasmic Disturbance	2-9%	0-1%

There are no adequate and well-controlled studies examining sexual dysfunction with paroxetine treatment.

Paroxetine treatment has been associated with several cases of priapism. In those cases with a known outcome, patients recovered without sequelae.

While it is difficult to know the precise risk of sexual dysfunction associated with the use of SSRIs, physicians should routinely inquire about such possible side effects.