Pregabalin in neuropathic pain - 2010 update

Clinical bottom line

Pregabalin has been studies in large, long duration studies, and in four neuropathic pain conditions, including fibromyalgia. It has useful levels of efficacy in all the conditions, with NNTs of 3-5 in neuropathic pain, and around 9 in fibromyalgia.

References

There are three reviews of pregabalin that provide information that is useful, but for the purposes of this 2010 update on efficacy, the Cochrane review is that from which data have been taken.

Moore et al.Pregabalin for acute and chronic pain in adults. Cochrane Database Syst Rev. 2009 Jul 8;(3):CD007076.
Straube et al. Pregabalin in fibromyalgia--responder analysis from individual patient data. BMC Musculoskelet Disord. 2010 Jul 5;11:150..
Straube et al. Pregabalin in fibromyalgia: meta-analysis of efficacy and safety from company clinical trial reports. Rheumatology (Oxford). 2010 49:706-715.

Study

Date review completed: 2009
Number of trials included: 25
Number of patients: 7003 in chronic pain
Control group: placebo
Main outcomes: responder analysis at various levels of response

Results

The trials in chronic pain were predominantly of long duration (typically 12 weeks, apart from occasional shorter studies, though these were about 8 weeks; sensitivity analyses reported that limiting analysis to studies of 8 weeks or longer made no appreciable difference to efficacy. Responders were identified in most trials, and as best can be judged these were probably using the last observation carried forward method. A variety of daily doses were used, 150 mg, 300 mg, 450 mg (in fibromyalgia) , and 600 mg, usually with a degree of titration up to the maximum daily dose.

Results tabulated below are the main efficacy findings

Postherpetic neuralgia

	Number of		Percent with outcome
Outcome - daily dose	Trials	Patients	Pregabalin	Placebo	Relative benefit or risk (95% CI)	NNT (95%CI)
At least 30% pain relief
150 mg	1	180	39	17	2.3 (1.4 to 3.8)	4.6 (2.9 to 11)
300 mg	2	369	49	24	2.1 (1.5 to 2.7)	4.0 (2.9 to 6.5)
600 mg	3	537	62	24	2.5 (2.0 to 3.2)	2.7 (2.2 to 3.4)
At least 50% pain relief
150 mg	3	527	25	11	2.3 (1.6 to 3.4	6.9 (4.8 to 13)
300 mg	4	713	32	13	2.5 (1.9 to 3.4)	5.1 (3.9 to 7.4)
600 mg	4	732	41	15	2.7 (2.1 to 3.5)	3.9 (3.1 to 5.1)
PGIC much or very much improved
150 mg	2	342	27	15	1.8 (1.2 to 2.8)	8.4 (4.9 to 30)
300 mg	2	348	32	15	2.2 (1.4 to 3.3)	5.8 (3.9 to 12)
600 mg	1	183	37	16	2.3 (1.3 to 3.9)	4.9 (3.0 to 12)
Lack of efficacy discontinuation
150 mg	3	527	8	13	0.6 (0.3 to 1.0)
300 mg	4	713	4	11	0.4 (0.2 to 0.7)	-15 (-9 to -34)
600 mg	4	732	3	11	0.3 (0.1 to 0.5)	-13 (-9 to -24)

Note that a negative NNT for lack of efficacy discontinuation means that this occurs less often with pregabalin than with placebo.

Painful diabetic neuropathy

	Number of		Percent with outcome
Outcome - daily dose	Trials	Patients	Pregabalin	Placebo	Relative benefit or risk (95% CI)	NNT (95%CI)
At least 30% pain relief
150 mg
300 mg	2	482	59	45	1.3 (1.1 to 1.6)	6.8 (4.3 to 17)
600 mg	3	819	63	43	1.5 (1.3 to 1.7)	5.1 (3.8 to 7.8)
At least 50% pain relief
150 mg	2	359	27	23	1.1 (0.8 to 1.6)	not calculated
300 mg	4	823	40	26	1.5 (1.2 to 1.8)	7.5 (5.1 to 14)
600 mg	6	1360	45	25	1.7 (1.5 to 2.0)	5.0 (4.0 to 6.6)
PGIC much or vey much improved
150 mg	1	195	45	34	1.4 (0.96 to 2.0)	not calculated
300 mg	2	359	48	30	1.6 (1.2 to 2.1)	5.6 (3.6 to 13)
600 mg	4	875	56	33	1.8 (1.5 to 2.1)	4.2 (3.3 to 5.8)
Lack of efficacy discontinuation
150 mg	2	359	4	7	0.7 (0.3 to 1.5)
300 mg	2	341	3	8	0.4 (0.2 to 1.0)
600 mg	4	869	4	11	0.3 (0.2 to 0.5)	-14 (-9 to -31)

Central neuropathic pain

	Number of		Percent with outcome
Outcome - daily dose	Trials	Patients	Pregabalin	Placebo	Relative benefit or risk (95% CI)	NNT (95%CI)
At least 30% pain relief
600 mg	1	136	42	13	3.1 (1.6 to 6.1)	3.5 (2.3 to 7.0)
At least 50% pain relief
600 mg	2	176	25	7	3.6 (1.5 to 8.4)	5.6 (3.5 to 14)
Lack of efficacy discontinuation
600 mg	2	177	6	24	0.3 (0.1 to 0.6)	-5.4 (-3.5 to -12)

Fibromyalgia

	Number of		Percent with outcome
Outcome - daily dose	Trials	Patients	Pregabalin	Placebo	Relative benefit or risk (95% CI)	NNT (95%CI)
At least 30% pain relief
150 mg	1	263	31	27	1.1 (0.8 to 1.7)
300 mg	4	1374	39	28	1.4 (1.2 to 1.6)	9.2 (6.3 to 17)
450 mg	4	1376	43	28	1.5 (1.3 to 1.8)	6.6 (5.0 to 9.8)
600 mg	3	1122	39	28	1.4 (1.2 to 1.6)	9.1 (6.1 to 18)
At least 50% pain relief
150 mg	1	263	13	13	1.0 (0.5 to 1.9)
300 mg	4	1374	21	14	1.5 (1.2 to 1.9)	14 (9.0 to 33)
450 mg	4	1376	25	14	1.7 (1.4 to 2.1)	9.8 (7.0 to 16)
600 mg	3	1122	24	15	1.6 (1.3 to 2.1)	11 (7.1 to 21)
PGIC much or very much improved
150 mg	1	263	32	27	1.2 (0.8 to 1.8)
300 mg	4	1374	36	28	1.5 (1.2 to 1.9)	11 (7.3 to 26)
450 mg	4	1376	42	28	1.5 (1.3 to 1.8)	6.8 (5.1 to 10)
600 mg	3	1122	41	28	1.5 (1.2 to 1.7)	7.7 (5.4 to 13)
PGIC very much improved
150 mg
300 mg	4	1352	17	11	1.7 (1.2 to 2.9)	16 (9.9 to 37)
450 mg	4	1354	19	11	1.8 (1.4 to 2.4)	11 (7.9 to 20)
600 mg	3	1095	12	7	1.7 (1.1 to 2.4)	21 (12 to 83)
Lack of efficacy discontinuation
150 mg	1	263	9	14	0.7 (0.3 to 1.3)
300 mg	4	1374	4	10	0.4 (0.3 to 0.7)	-18 (-12 to -34)
450 mg	4	1376	3	10	0.3 (0.2 to 0.5)	-15 (-11 to -25)
600 mg	3	1122	2	9	0.3 (0.2 to 0.5)	-15 (-11 to -26)

Efficacy figures

The figures show the NNTs for the four clinical conditions, for 300 mg and 600 mg daily using at least 30% and at least 50% pain intensity reduction

Pregabalin 300 mg daily, at least 30% pain reduction

Pregabalin 300 mg daily, at least 50% pain reduction

Pregabalin 600 mg daily, at least 30% pain reduction

Pregabalin 600 mg daily, at least 50% pain reduction

Adverse events

Adverse events of somnolence, dizziness, and adverse event discontinuations were also reported for the four clinical conditions. Typically they were dose dependent, and typical event rates and NNTs were as follows:

Somnolence

Somnolence tended to occur in 15--20% of patients on pregabalin 300-600 mg daily, with rates of about 5% with placebo, with NNH values of 6-8. The exception was central neuropathic pain with much higher rates and with an NNH of 4.

Dizziness

Dizziness tended to occur in 25--45% of patients on pregabalin 300-600 mg daily, with rates of about 10% with placebo, with NNH values of about 4.

Adverse event withdrawal

Adverse event withdrawal tended to occur in 15--30% of patients on pregabalin 300-600 mg daily, with rates of about 5-10% with placebo, with NNH values of about 10.

Serious adverse events

Serious adverse events were no more frequent with pregabalin than placebo.