PAXIL Study 329 - source GSK - Study 329 SEROXAT

http://www.gsk.com/media/paroxetine/letter.pdf


Study 329 long-term, continuation phase: After 8 weeks of the acute-phase treatment, a second phase


of Study 329 was conducted where patients defined as responders (HAM-D ≤8 at week 8 or a ≥50%

decrease in HAM-D from baseline) could be continued on the same medication in a double-blind manner

for a 6-month continuation treatment phase.(11) The objectives were to provide information on the safety
 
 
profile of Paxil Tablets and imipramine when given to adolescents for an extended period of time and to


estimate the rate of relapse among responders maintained on treatment. The continuation phase of this

study was not designed to analyze efficacy, as patients were not re-randomized at the end of the acute

phase. The proportion of patients relapsing at any time during the continuation phase (regardless of

HAM-D at endpoint) was 38.7% for the imipramine group, 36.4% for the Paxil Tablets group, and 23.1%

for the placebo group. There were no significant differences between Paxil Tablets (13.5%) and placebo

(18.2%) or between imipramine (15%) and placebo (18.2%) in withdrawals due to lack of efficacy.

Adverse events are presented in Table 1.(11) Serious adverse events during the continuation phase occurred

in 9 patients (6 receiving Paxil Tablets, 2 on imipramine, and 1 on placebo). Serious events in patients

receiving Paxil Tablets were peptic ulcer hemorrhage (n = 1), intentional overdose (n = 3), and manic

reaction (n = 1); one patient experienced agitation, fatigue, nausea, drowsiness, and tremor after missing

some doses of taper medication. In the imipramine group, 1 patient developed tricyclic toxicity and

another took an intentional overdose. In the placebo group, 1 patient had homicidal and suicidal ideations.

Four patients (7.7%) treated with Paxil Tablets, 8 patients (20%) in the imipramine group, and 4 patients

(12.1%) in the placebo group dropped out due to an adverse event. Adverse events related to the nervous

system and leading to withdrawal occurred in 3 patients in the Paxil Tablets group (for emotional lability

[e.g., suicidal ideation/gestures]), 3 patients in the imipramine group (1 for emotional lability [e.g., suicidal

ideation/gestures], 1 for neurosis, and 1 for convulsion), and 1 patient in the placebo group (for emotional

lability [e.g., suicidal ideation/gestures], hostility, and manic reaction). All other events leading to

withdrawal occurred in ≤1 patient in any group.

Table 1. Adverse Events Occurring in ≥5% of Paxil Tablets and Imipramine Groups and Twice the

Rate of Placebo (approximately 4 months of exposure for each group)(11)

Paxil Tablets Imipramine Placebo

Adverse Event N = 52

n (%)

N = 40

n (%)

N = 33

n (%)

Abdominal pain 6 (11.5%) 4 (10%) 1 (3%)

Weight gain 4 (7.7%) 1 (2.5%) 0 (0%)

Emotional lability (e.g.,

suicidal ideation/gestures)

4 (7.7%) 1 (2.5%) 1 (3%)

Insomnia 4 (7.7%) 3 (7.5%) 1 (3%)

Tremor 3 (5.8%) 0 (0%) 0 (0%)

Tachycardia 1 (1.9%) 2 (5%) 0 (0%)

Dry mouth 1 (1.9%) 3 (7.5%) 0 (0%)

Myalgia 1 (1.9%) 3 (7.5%) 0 (0%)

Dyspepsia 0 (0%) 2 (5%) 0 (0%)

Combing the safety data for the acute phase and continuation phases of Study 329 showed that emotional

lability (e.g., suicidal ideation/gestures) was the only serious adverse event reported in the Paxil Tablets

group at an incidence ≥5% and twice the rate of placebo.(11) Serious adverse events of emotional lability

(e.g., suicidal ideation/gestures) were reported in 5 patients treated with Paxil Tablets (5.4%) during the

acute phase and 3 patients treated with Paxil Tablets (5.8%) in the continuation phase; of these, 1 patient

had a serious adverse event of emotional lability (e.g., suicidal ideation/gestures) in both phases.