Table 6 Relevant pharmacogenetics association studies that focused on the serotonin transporter promoter (5HTTLPR)

[31]

5HTTLPR

Lithium augmentation

47 lithium-treated patients 114 lithium-free patients

HAMD

Patients homozygous for the short allele had a more favourable response compared with those who were heterozygous

p = 0.0002

[61]

5HTTLPR

Paroxetine

110 elderly MDD patients

HAMD

Paroxetine concentrations were correlated with change in HAMD scores after two weeks of treatment in subjects with the short allele (elderly population)

p < 0.05

[50]

5HTTLPR

Paroxetine

166 depressed patients

HAMD

5-HTTLPR short allele homozygotes were significantly associated with both remission and response. Unipolar patients homozygous for the SLC6A4 intron 2 repeat polymorphism were significantly associated with lack of remission and lack of response

Remission

p = 0.04

Response

p = 0.02

Lack of remission

p = 0.02

Lack of response

p = 0.01

[62]

5HTTLPR

Various

190 depressed patients

HAMD

SLC6A4: no association

Not significant

[35]

5HTTLPR

Citalopram

1775 patients with non-psychotic depression (STAR*D)

Categorical response and remission at HAMD, tolerance, and adverse effect burden

A significant association between the L(A) allele and adverse effect burden was detected. A lesser adverse effect burden was associated with L(A)L(A) genotype frequency

p = 0.004 (whole sample)

p = 0.03 (Caucasians only)

[63]

5HTTLPR

Fluoxetine or sertraline or nortriptyline

241 depressed patients

HAMD

Short allele of the intron 2 variation was associated with better response; short allele at the 5HTTLPR was associated with response

p <0.001 (nortriptyline);

p = 0.006 (SSRIs)

[34]

5HTTLPR

Fluvoxamine

228 patients (with either bipolar or unipolar depression)

HAMD

Long (l) variant associated with better and faster response; 16F *l → partial response, 16D *l → better response than 16A *l

p = 0.047

[64]

5HTTLPR

Various

109 patients with major depression

DOTES

HTT-VNTR 2.10/2.10 associated with higher frequency of side effects; HTTLPR s/s associated with higher frequency of side effects

p = 0.00018

[65]

5HTTLPR

Fluoxetine

224 depressed patients

HAMD

5HTTLPR l/l associated with a better response

p <0.001

[66]

5HTTLPR

Fluoxetine and paroxetine

100 depressed patients

HAMD

5HTTLPR: long allele associated with better response

p = 0.015-0.042

[46]

5HTTLPR

Citalopram

130 depressed patients

HAMD

S/S-G/G haplotype was found among subjects who did not reach remission

p = 0.009

[67]

5HTTLPR

Various

128 patients with bipolar disorder, 93 patients with unipolar disorder

HAMD

No association

Not significant

[68]

5HTTLPR

Milnacipram

96 depressed patients

MADRS

No association

Not significant

[57]

5HTTLPR

Fluvoxamine or paroxetine

220 depressed patients

HAMD

SERT s/s associated with poorer response to treatment; TPH no significant result

p = 0.034

[69]

5HTTLPR

Long-term antidepressant treatment

128 depressed patients

CGI

s/s genotype was associated with poorer outcome

p = 0.025

[48]

5HTTLPR

Fluoxetine

96 depressed patients

HAMD

A single variation showed a marginal association with antidepressant response

p = 0.037

[70]

5HTTLPR

Sertraline

103 depressed patients and 103 placebo controls

HAMD and CGI

Short allele associated with slower response

p = 0.01

[71]

5HTTLPR

Citalopram

131 depressed patients

HAMD

s/s geneotype associated with non remission

p = 0.006

[72]

5HTTLPR

Fluoxetine or nortriptyline

169 depressed patients

MADRS

< 25 years: no association; >25 years: HTTLPR s/s genotype associated with a poorer response to both fluoxetine and nortriptyline

p = 0.026

[73]

5HTTLPR

Fluoxetine

121 depressed patients

HAMD

l/l genotype shows a better response

p = 0.013

[74]

5HTTLPR

Fluvoxamine

155 depressed patients

HAMD

Long allele subjects were more likely to respond

p = 0.029

[75]

5HTTLPR

SSRI, TCA

27 bipolar patients with at least one manic episode triggered by SSRIs and 29 bipolar patients who had not

Presence of manic episode induced by serotonergic antidepressant

Patients with manic or hypomanic episodes induced by antidepressant treatment had an excess of short alleles

p <0.001

[76]

5HTTLPR

Various antidepressants

173 depressed patients

HAMD

No association with antidepressant response

Not significant

[4]

5HTTLPR

Fluvoxamine

217 depressed patients

HAMD

A/A genotype was associated with slower response in patients not taking pindolol

p = 0.001

[36]

5HTT Stin2 5HTTLPR

Fluoxetine, paroxetine

120 patients and 252 controls

HAMD

l/l in intron 2 was associated with better response to treatment s/s genotype showed better response

p <0.0001

p = 0.0074