Serotonin transporter polymorphisms and adverse effects with fluoxetine treatment.
BACKGROUND
The short (S) allele of the serotonin transporter gene-linked polymorphic region (5HTTLPR) has been associated with poorer antidepressant response in major depressive disorder (MDD) and with antidepressant-induced mania. This study investigated a possible association with treatment-emergent insomnia or agitation.


METHODS
Thirty-six outpatients with MDD were genotyped at 5HTTLPR and treated with open-label fluoxetine up to 60 mg/day. Treatment-emergent adverse effects were assessed at each study visit.


RESULTS
Of nine subjects homozygous for the "S" allele, seven (78%) developed new or worsening insomnia, versus 6 of 27 (22%) non-"S"-homozygous subjects (Fisher's exact p =.005). Similarly, six of nine subjects homozygous for the "S" allele (67%) developed agitation, versus 2 of 27 (7%) of non-"S"-homozygous subjects (Fisher's exact p =.001).


CONCLUSIONS
The "S" allele of the 5HTTLPR may identify patients at risk for developing insomnia or agitation with fluoxetine treatment. This preliminary result requires confirmation in larger samples.
Department of Psychiatry, Massachusetts General Hospital, Boston 02114, USA.
Roy H
RH
Perlis
David
D
Mischoulon
Jordan W
JW
Smoller
Yu-Jui Yvonne
YJ
Wan
Stefania
S
Lamon-Fava
Keh-Ming
KM
Lin
Jerrold F
JF
Rosenbaum
Maurizio
M
Fava
D000328:Adult; D000483:Alleles; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects* / Q000627:therapeutic use; D002352:Carrier Proteins / Q000235:genetics*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D005260:Female; D005473:Fluoxetine / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D011110:Polymorphism, Genetic; D011595:Psychomotor Agitation / Q000209:etiology; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D007319:Sleep Initiation and Maintenance Disorders / Q000139:chemically induced
D018687:Antidepressive Agents, Second-Generation; D002352:Carrier Proteins; D005473:Fluoxetine; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human