Comparing effects of methylphenidate, sertraline and placebo on neuropsychiatric sequelae in patients with traumatic brain injury

Hum Psychopharmacol. 2005 Mar;20(2):97-104. doi: 10.1002/hup.668.


Background: This study aimed to investigate the effects of methylphenidate and sertraline compared with placebo on various neuropsychiatric sequelae associated with traumatic brain injury (TBI).

Methods: This was a 4 week, double-blind, parallel-group trial. Thirty patients with mild to moderate degrees of TBI were randomly allocated to one of three treatment groups (n = 10 in each group) with matching age, gender and education, i.e. methylphenidate (starting at 5 mg/day and increasing to 20 mg/day in a week), sertraline (starting at 25 mg/day and increasing to 100 mg/day in a week) or placebo. At the baseline and at the 4 week endpoint, the following assessments were administered: subjective (Beck Depression Inventory) and objective (Hamilton Depression Rating Scale) measures of depression; Rivermead Postconcussion Symptoms Questionnaire for postconcussional symptoms; SmithKline Beecham Quality of Life Scale for quality of life; seven performance tests (Critical Flicker Fusion, Choice Reaction Time, Continuous Tracking, Mental Arithmetic, Short-Term memory, Digit Symbol Substitution and Mini-Mental State Examination); subjective measures of sleep (Leeds Sleep Evaluation Questionnaire) and daytime sleepiness (Epworth Sleepiness Scale). All adverse events during the study period were recorded and their relationships to the drugs were assessed.

Results: Neuropsychiatric sequelae seemed to take a natural recovery course in patients with traumatic brain injury. Methylphenidate had significant effects on depressive symptoms compared with the placebo, without hindering the natural recovery process of cognitive function. Although sertraline also had significant effects on depressive symptoms compared with the placebo, it did not improve many tests on cognitive performances. Daytime sleepiness was reduced by methylphenidate, while it was not by sertraline.

Conclusions: Methylphenidate and sertraline had similar effects on depressive symptoms. However, methylphenidate seemed to be more beneficial in improving cognitive function and maintaining daytime alertness. Methylphenidate also offered a better tolerability than sertraline.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antidepressive Agents / administration & dosage
  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / therapeutic use
  • Central Nervous System Stimulants / administration & dosage
  • Central Nervous System Stimulants / adverse effects
  • Central Nervous System Stimulants / therapeutic use
  • Cognition Disorders / drug therapy
  • Depression / complications
  • Depression / drug therapy*
  • Depression / physiopathology
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Methylphenidate / administration & dosage
  • Methylphenidate / adverse effects
  • Methylphenidate / therapeutic use*
  • Patient Selection
  • Post-Concussion Syndrome / complications
  • Post-Concussion Syndrome / drug therapy*
  • Post-Concussion Syndrome / physiopathology
  • Prospective Studies
  • Psychiatric Status Rating Scales / statistics & numerical data
  • Psychological Tests / statistics & numerical data
  • Quality of Life / psychology
  • Sertraline / administration & dosage
  • Sertraline / adverse effects
  • Sertraline / therapeutic use*
  • Sleep / drug effects
  • Sleep Stages / drug effects
  • Sleep Stages / physiology
  • Treatment Outcome


  • Antidepressive Agents
  • Central Nervous System Stimulants
  • Methylphenidate
  • Sertraline