Critical appraisal of paroxetine for the treatment of vasomotor symptoms

Figures & data

Table 1 Instruments used in trials to assess vasomotor symptoms (VMS)

Instrument	Score	Clinical interpretation
Hot Flash Composite Score^Citation11	Each level of hot flash severity (mild =1, moderate =2, severe =3, very severe =4) × daily number of hot flashes in that category A daily score is compiled from the sum of the four resulting values	Higher scores correlate with more severe symptoms
Greene Climacteric Scale^Citation12 (validated)	Consists of 21 items scored as not at all =0, a little =1, quite a bit =2, extremely =3 to assess four domains: psychological (items 1–11; score range 0–33), somatic (12–18; 0–21), VMS (19–20; 0–6), and sexual dysfunction (21; 0–3)	Score range: 0–63 (higher scores correlate with more severe symptoms); VMS subscore: 0–6 (scores of 0–2 indicate no to mild hot flashes, and scores of 3–6 indicate moderate-to-severe hot flashes)
Weekly hot flash severity score^Citation10	Mild = sensation of heat without sweating Moderate = sensation of heat with sweating, able to continue activity Severe = sensation of heat with sweating, causes cessation of activity (2× number of moderate) + (3× number of severe) divided by the total number of moderate and severe	Higher scores correlate with more severe symptoms
Patient Global Impression of Improvement^Citation11,Citation16 (validated)	“Compared to before starting the study medication, how would you describe your hot flushes now?”	Satisfied = (1) Very much better or (2) Much better
	(1) Very much better, (2) Much better, (3) A little better, (4) No change, (5) A little worse, (6) Much worse, (7) Very much worse	Unsatisfied = otherwise

Table 2 Summary of the literature on paroxetine for treatment of vasomotor symptoms in patients primarily with a history of breast cancer

Study design	Patient characteristics	Treatment regimen and duration	Efficacy results
Open-label study (n=30)^Citation13	History of breast cancer without detectable disease; mean age: 52 years; mean hot flashes/day: eight	Paroxetine HCl 10 mg daily for 1 week, followed by 20 mg daily for 5 weeks	Significant decreases in hot flash frequency (67%; CI: 56%–79%); significant decreases in hot flash scores (75%; CI: 66%–85%)
Open-label study(n=13)^Citation14	History of breast cancer with adjunctive chemotherapy in past 6 months; mean age: 52 years; mean hot flashes/day: NR	Paroxetine HCl 10 mg daily for 3 days, followed by 20 mg daily thereafter for 6 weeks	Hot flash severity score: 3.62±0.51 (pre) vs 2.08±1.32 (post); P=0.002
Randomized, double-blind, placebo-controlled, crossover study (n=151)^Citation15	Women with or without a history of breast cancer; median age: 53 years; mean hot flashes/day: seven to eight	Arm 1: paroxetine HCl 10 mg daily crossover to placebo; Arm 2: paroxetine HCl 20 mg daily crossover to placebo; Arm 3: placebo crossover to paroxetine HCl 10 mg daily; Arm 4: placebo crossover to paroxetine HCl 20 mg daily. Each treatment period was of 4 weeks’ duration, with a 1-week washout between arms	Hot flash frequency reduction: 40.6% (SE: 5.1%) with paroxetine 10 mg vs 13.7% (SE: 5.6%) with placebo, P=0.0006; 51.7% (SE: 5.3%) with paroxetine 20 mg vs 26.6% (SE: 7.0%), P=0.002 Hot flash composite score reduction: 45.6% (SE: 5.8%) with paroxetine 10 mg vs 13.7% (SE: 6.9%) with placebo, P=0.0008; 56.1% (SE: 6.7%) with paroxetine 20 mg vs 28.5% (SE: 7.9%), P<0.001

Abbreviations: CI, confidence interval; NR, not reported; SE, standard error; HCl, hydrochloride.

Table 3 Summary of the literature on paroxetine for treatment of vasomotor symptoms in patients primarily without a history of breast cancer

Study design	Patient characteristics	Treatment regimen and duration	Efficacy results
Randomized, double-blind, placebo-controlled trial (n=165)^Citation11	Menopausal women with or without history of breast cancer (7% with history of breast cancer); mean age: 54–55 years; mean hot flashes/day: six to seven	Paroxetine HCl CR 12.5 mg or 25 mg daily vs placebo ×6 weeks	Significant decreases in hot flash scores in both 12.5 mg and 25 mg groups vs placebo (62.2% vs 37.8%, P=0.007 and 64.6% vs 37.8%, P=0.03, respectively)
Randomized, double-blind, placebo-controlled trial (n=56)^Citation12	Menopausal women; mean age: 56–57 years; median hot flashes/week: 17	Paroxetine HCl CR 12.5 mg daily vs placebo ×6 weeks; may increase to 25 mg daily at 2 weeks based on treatment response and tolerability	Median weekly reductions in hot flashes: 6.1 (IQR: 2.7–6.8) with paroxetine vs 2.8 (IQR: 0.1–4.5) with placebo; P=0.03 GCS scores for VMS also significantly decreasedbut scores NR; P=0.04 63% increased paroxetine dose to 25 mg/day
Randomized, double-blind, placebo-controlled trial (n=614)^Citation10	Postmenopausal women with moderate-to-severe VMS; median age: 54 years; mean hot flashes/day: eleven	Paroxetine mesylate 7.5 mg daily vs placebo ×12 weeks	Mean weekly reductions in hot flashes: 43.5 with paroxetine vs 37.3 with placebo, P=0.009 Hot flash severity scores significantly decreased at Week 4 (P=0.0048) but not at Week 12 (P=0.2893)
Randomized, double-blind, placebo-controlled trial (n=570)^Citation10	Postmenopausal women with moderate-to-severe VMS; median age: 54 years; mean hot flashes/day: eleven	Paroxetine mesylate 7.5 mg daily vs placebo ×24 weeks	Mean weekly reductions in hot flashes: 37.2 with paroxetine vs 27.6 with placebo, P=0.0001 Hot flash severity scores significantly decreased at both Week 4 (P=0.0452) and Week 12 (P=0.0114) Persistence of treatment effect was observed in 47.5% with paroxetine vs 36.3% with placebo at 24 weeks (P=0.0066)

Abbreviations: CR, controlled release; GCS, Greene Climacteric Score; HCl, hydrochloride; IQR, interquartile range; NR, not reported; VMS, vasomotor symptoms.

Table 4 Available paroxetine formulations in the USA and associated cost

Drug	Available formulations	AWP cost (30-day supply)
Paroxetine HCl	Generic 10 mg, 20 mg, 30 mg, 40 mg tablets	$78.56 (10 mg)
	Generic CR 12.5 mg, 25 mg, 37.5 mg tablets	$108.63 (12.5 mg)
	aPaxil 10 mg, 20 mg, 30 mg, 40 mg tablets	$163.85 (10 mg)
	aPaxil CR 12.5 mg, 25 mg, 37.5 mg tablets	$168.76 (12.5 mg)
	aPaxil 10 mg/5 mL suspension	$284.45 (250 mL)
Paroxetine mesylate	bBrisdelle 7.5 mg capsules	$161.64
	bPexeva 10 mg, 20 mg, 30 mg, 40 mg tablets	$265.74 (10 mg)

Notes:

a Notes: GlaxoSmithKline LLC, Research Triangle Park, NC, USA;

b Noven Therapeutics, LLC, Miami, FL, USA. Adapted with permission from Paroxetine. In: RED BOOK [AUHSOP intranet database]. Greenwood village, CO: Truven Health Analytics [updated daily]. Available from: http://www.micromedexsolutions.com/micromedex2/librarian/ND_T/evidencexpert/ND_PR/evidencexpert/CS/9F9DDB/ND_AppProduct/evidencexpert/DUPLICATIONSHIELDSYNC/49D885/ND_PG/evidencexpert/ND_B/evidencexpert/ND_P/evidencexpert/PFActionId/redbook.FindRedBook?navitem=topRedBook. Accessed December 14, 2014.³⁴

Abbreviations: AWP, average wholesale price; CR, controlled release; HCl, hydrochloride.

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