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.
Perlis
Roy H
RH
Department of Psychiatry, Massachusetts General Hospital, Boston 02114, USA.
Mischoulon
David
D
Smoller
Jordan W
JW
Wan
Yu-Jui Yvonne
YJ
Lamon-Fava
Stefania
S
Lin
Keh-Ming
KM
Rosenbaum
Jerrold F
JF
Fava
Maurizio
M
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