Table 6.
Relevant pharmacogenetics association studies that focused on the serotonin transporter promoter (5HTTLPR)
| Reference | Gene | Drug | Sample | Outcome measure | Results | p-value |
|---|---|---|---|---|---|---|
| [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 |
Abbreviations: 5HTTLPR, serotonin promoter polymorphism; MDD, major depressive disorder; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant; HAMD, Hamilton Rating Scale for Depression; DOTES, dosage record and treatment emergent symptom; HTT-VNTR, variable number of tandem repeats (VNTR) within serotonin transporter; MADRS, Montgomery-Asberg Depression Rating Scale