Table 6

Relevant pharmacogenetic association studies that focused on 5-HTTLPR

Study	Gene	Drug	Results	Quality (0–31)	Sample size
Mrazek et al.175	5-HTTLPR	Citalopram	White non-Hispanic: Int2 VNTRs 12/12 and LL genotype ↑ remission	25	1914
Yoshimura et al.186	5-HTTLPR	Paroxetine	No association	21	60
Gressier et al.213	5-HTTLPR	Various antidepressants	In females L allele ↑ response	19	103
Min et al.191	5-HTTLPR	SSRI, SNRI	5-HTTLPR L/L or STin2 12/12 genotype ↑ response to SSRI	25	657
Huezo-Diaz et al.174	5-HTTLPR	Escitalopram, nortriptyline	L allele ↑ response to escitalopram, > effect in males	20	795
Capozzo et al.214	5-HTTLPR	Citalopram	l/l carriers ↑ response	8	21
Maron et al.180	5-HTTLPR	Escitalopram	No associations in response S allele ↑ severe headache	20	135
Wilkie et al.179	5-HTTLPR	Paroxetine	SLC6A4 intron 2 repeat homozygosis ↓ remission and response	11	163
Benedetti et al.194	5-HTTLPR	Lithium augmentation	s/s genotype ↑ response	21	161
Bozina et al.173	5-HTTLPR	Paroxetine	L allele and STin2 10/10 ↑ response	21	130
Dogan et al.178	5-HTTLPR	Sertraline	No association	NA	64
Ferreira et al.215	5-HTTLPR	Various	L allele ↓ switch into a manic episode	9	112
Oberlander et al.196	5-HTTLPR	SSRIs exposed neonates	l/l genotype ↑ respiratory symptoms (respiratory distress and rapid breathing) s/s genotype ↑ neuromotor symptoms	13	37
Lotrich et al.192	5-HTTLPR	Paroxetine	In s carriers paroxetine concentrations ↑ response (elderly population)	16	110
Schillani et al.216	5-HTTLPR	Sertraline	L carriers ↑ response	10	11
Smits et al.163	5-HTTLPR	Various SSRIs	In female s-allele ↓ response	13	214
Stamm et al.193	5-HTTLPR	Lithium augmentation	s/s genotype ↑ response	14	55
Tanaka et al.217	5-HTTLPR	Paroxetine	No association with iatrogenic nausea	15	72
Kang et al.181	5-HTTLPR	Mirtazapine	s/s genotype ↑ response	18	101
Kirchheiner et al.218	5-HTTLPR	Various	No association	19	77
Kronenberg et al.219	5-HTTLPR	Citalopram	In children l /l genotype ↑ response	24	312
Hu et al.177	5-HTTLPR	Citalopram	L(A) allele ↑ side effects	19	1655
Kim et al.184	5-HTTLPR	Fluoxetine sertraline notriptyline	STin2 12/12 ↑ response to SSRIs S allele ↑ response to SSRIs and to nortriptyline	19	208
Masoliver et al.220	5-HTTLPR	Various antidepressants	s alleles ↑ manic switch	8	188
Ng et al.221	5-HTTLPR	Sertraline	No association with response and side effects	16	35
Smeraldi et al.208	5-HTTLPR	Fluvoxamine	l allele ↑ response 16F l ↑ partial response 16D l ↑ response	21	228
Popp et al.206	5-HTTLPR	Various	STin2 10/10 ↑ side effects s/s genotype ↑ side effects	9	109
Hong et al.83	5-HTTLPR	Fluoxetine	l/l genotype ↑ response	15	224
Kato et al.190	5-HTTLPR	Fluoxetine paroxetine	l/l genotype ↑ response	17	100
Kraft et al.207	5-HTTLPR	Fluoxetine	rs25531 ↑ response	16	96
Kato et al.189	5-HTTLPR	Fluvoxamine paroxetine	l allele ↑ response to fluvoxamine	18	81
Arias et al.222	5-HTTLPR	Citalopram	S/S-G/G haplotype ↓ remission	18	130
Serretti et al.119	5-HTTLPR	Various	No association	22	185
Yoshida et al.185	5-HTTLPR	Milnacipram	No association	17	96
Serretti et al.120	5-HTTLPR	Fluvoxamine, paroxetine	s/s genotype ↓ response	22	221
Serretti et al.223	5-HTTLPR	Various antidepressants	No association with manic switch	17	416
Lee et al.188	5-HTTLPR	Long-term antidepressants	s/s genotype ↓ response	12	128
Peters et al.85	5-HTTLPR	Fluoxetine	rs25533 in STin2 ↑ response	19	96
Murphy et al.171	5-HTTLPR	Paroxetine, mirtazapine	l allele ↑ response and ↓ side effects to paroxetine but ↑ side effects to mirtazapine	18	246
Durham et al.172	5-HTTLPR	Sertraline	S allele ↓ response	18	206
Arias et al.169	5-HTTLPR	Citalopram	s/s genotype ↓ remission	18	131
Joyce et al.170	5-HTTLPR	Fluoxetine, nortriptyline	< 25 yr: no association > 25 yr: s/s genotype ↓ response	15	139
Perlis et al.224	5-HTTLPR	Fluoxetine	s/s genotype ↑ response s allele ↑ insomnia or agitation	19	36
Rousseva et al.225	5-HTTLPR	Antidepressants	No association with manic switch	12	305
Takahashi et al.121	5-HTTLPR	Fluvoxamine	No association with fluvoxamine induced nausea	21	54
Yu et al.187	5-HTTLPR	Fluoxetine	l/l genotype ↑ response	15	121
Rausch et al.168	5-HTTLPR	Fluoxetine	l/l subjects ↑ rapid response	19	51
Ito et al.205	5-HTTLPR	Fluvoxamine	No association (STin2)	15	54
Yoshida et al.183	5-HTTLPR	Fluvoxamine	s allele ↑ response	14	54
Zanardi et al.166	5-HTTLPR	Fluvoxamine	l allele ↑ response	21	64
Arias et al.226	5-HTTLPR	Citalopram	s/s genotype ↓ response	18	269
Mundo et al.227	5-HTTLPR	SSRI, TCA	s allele ↑ manic or hypomanic switch	15	27
Minov et al.176	5-HTTLPR	Various antidepressants	No association	9	104
Serretti et al.77	5-HTTLPR	Fluvoxamine	l allele ↑ response	22	217
Zanardi et al.165	5-HTTLPR	Paroxetine	s allele ↓ response	18	58
Pollock et al.167	5-HTTLPR	Paroxetine	s allele ↑ slower response	16	57
Kim et al.182	5-HTTLPR	Fluoxetine, paroxetine	s/s genotype and L/L in intron ↑ response	14	120
Smeraldi et al.164	5-HTTLPR	Fluvoxamine	l allele ↑ response	16	53

↑ = positive association; ↓ = negative association; SNRI = serotonin–norepinephrine reuptake inhibitor; SSRI = selective serotonin reuptake inhibitor; TCA = tricyclic antidepressant; VNTR = variable number tandem repeat.