Influence of serotonergic/noradrenergic gene polymorphisms on nausea and sweating induced by milnacipran in the treatment of depression

Figures & data

Table 1 Adverse events induced by milnacipran treatment (N = 80)

	Number of patients	(%)
Nausea	10	12.5
Increased sweating	10	12.5
Headache	7	8.8
Constipation	5	6.3
Palpitation	4	5.0
Dry mouth	3	3.8
Discomfort of head	3	3.8
Chill or heat of leg or arms	3	3.8
Sleep disturbance	2	2.5
Bitterness	1	1.3
Inner tension/anxiety	1	1.3
Blurred vision	1	1.3
Stomach ache	1	1.3
Urinary hesitancy	1	1.3
Tremor	1	1.3
Diarrhea	1	1.3
Skin tingling	1	1.3

Table 2 Clinical characteristic of patients with and without nausea (N = 80)

	Nausea (+) (N = 10)	Nausea (−) (N = 70)	p value
Sex (male/female)	5/5	25/49	p = 0.31
Age (year)a	53.4 ± 14.7	51.1 ± 11.9	p = 0.59
Number of previous episodesa	0.1 ± 0.3	0.4 ± 1.1	p = 0.42
Melancholia (±)	2/8	22/48	p = 0.71
MADRS score at baseline	28.4 ± 5.4	28.6 ± 6.2	p = 0.61

Notes:

a Data are expressed as mean ± SD. A p value lower than 0.05 is defined as statistically significant.

Table 3 genotype distributions in patients with and without nausea (N = 80)

Group	Genotype distribution (N)			p value
5-HTT LPR
	S/S	S/L	L/L
Nausea (+)	5	4	0	χ^2 = 0.70
Nausea (−)	46	23	2	p = 0.70
5-HTT VNTR
	12/12	12/10	10/10
Nausea (+)	7	2	0	χ^2 = 0.49
Nausea (−)	58	11	2	p = 0.78
5-HT2A G-1438A
	A/A	G/A	G/G
Nausea (+)	2	5	2	χ^2 = 0.48
Nausea (−)	22	31	18	p = 0.78
MAOA VNTR
	1/1	1/3	3/3
Nausea (+)	7	0	2	(−)
Nausea (−)	35	17	17	(−)
TPH A218C
	A/A	A/C	C/C
Nausea (+)	2	6	1	χ^2 = 1.7
Nausea (−)	19	32	20	p = 0.42
NET T-182C
	T/T	T/C	C/C
Nausea (+)	3	5	1	χ^2 = 0.43
Nausea (−)	27	40	4	p = 0.80
NET G1287A
	G/G	G/A	A/A
Nausea (+)	6	3	0	χ^2 = 1.9
Nausea (−)	32	32	7	p = 0.38

Notes: MAOA VNTR was excluded from analysis because of violation of Hardy–Weinberg equilibrium. A p value lower than 0.007 is defined as statistically significant (see text for detail).

Table 4 Clinical characteristics of the patients with and without sweating (N = 80)

	Sweating (+) (N = 10)	Sweating (−) (N = 70)	p value
Sex (male/female)	4/6	24/46	p = 0.73
Age (year)a	59.6 ± 7.9	50.3 ± 12.3	* p = 0.03
Number of previous episodesa	0.33 ± 0.71	0.39 ± 1.11	p = 0.87
Melancholia (+/−)	3/7	21/49	p > 0.99
MADRS score at baseline	27.3 ± 5.8	28.8 ± 6.1	p = 0.75

Notes:

a Data are expressed as mean ± SD.

* A p value lower than 0.05 is defined as statistically significant.

Table 5 genotype distributions in patients with and without excessive sweating (N = 80)

Group	Genotype distribution (N)			p value
5-HTT LPR
	S/S	S/L	L/L
Sweating (+)	2	6	1	χ^2 = 8.5
Sweating (−)	48	22	1	p = 0.013
5-HTT VNTR
	12/12	12/10	10/10
Sweating (+)	6	3	0	χ^2 = 2.3
Sweating (−)	59	10	2	p = 0.31
5-HT2A G-1438A
	A/A	G/A	G/G
Sweating (+)	3	2	4	χ^2 = 2.7
Sweating (−)	21	34	16	p = 0.25
MAOA VNTR
	1/1	1/3	3/3
Sweating (+)	5	2	2	(−)
Sweating (−)	37	15	17	(−)
TPH A218C
	A/A	A/C	C/C
Sweating (+)	2	5	2	χ^2 = 0.26
Sweating (−)	19	33	19	p = 0.87
NET T-182C
	T/T	T/C	C/C
Sweating (+)	1	8	0	χ^2 = 4.4
Sweating (−)	29	37	5	p = 0.10
NET G1287A
	G/G	G/A	A/A
Sweating (+)	4	5	0	χ^2 = 1.2
Sweating (−)	34	30	7	p = 0.54

Notes: MAOA VNTR was excluded from analysis because of violation of Hardy–Weinberg equilibrium. A p value lower than 0.007 is defined as statistically significant (see text for detail).