SMTr-METAB : FDG-PET Assessment of Cerebral Metabolism in Resistant Depression Treated With rTMS
Condition: Depression
MeSH terms: Depression; Depressive Disorder
Study type: Interventional

Summary: 
      Biological markers of depressive states have been studied, but their usefulness to predict
      the therapeutic response is unknown. This issue is major in all depressive states which have
      not remitted after several lines of treatment. rTMS (repetitive transcranial magnetic
      stimulation) is a non-pharmacological alternative in the treatment of depression, but its
      effects on cerebral functioning are not known in episodes which have resist to conventional
      treatments. The investigators will include 50 depressive patients who have failed to respond
      to two successive antidepressant medication, and propose them a treatment with low frequency
      rTMS during 3 to 6 weeks. Cerebral functional imaging with 18FDG-PET (positon emission
      tomography) with be assessed at the beginning and at the end of rTMS acute treatment, in
      order to measure induced metabolic changes and their correlation with clinical states.
      Patients who have responded to rTMS acute treatment may continue this therapeutic for six
      months, and the investigators will assess if efficacy maintenance is related with cerebral
      metabolic variations
    

Detailed description: 
      In France, lifetime prevalence of depression is 21 %, with major consequences: handicap, loss
      of productivity, reduction in quality of life, increased mortality. The efficient and
      long-lasting care of depression is consequently a priority of public health.

      Despite well-conducted conventional therapeutic strategies, it is estimated that about 30 %
      of the depressed patients do not respond at all to an antidepressant, that 30 % will present
      a partial response, and that 40 % only patients will have a complete remission.

      Non-pharmacological alternative treatments have been promoted, particularly with repetitive
      transcranial magnetic stimulation (rTMS). A recent meta-analysis with 29 randomized
      controlled trials versus placebo reports a 29.3 % response rate and a 18.6 % remission rate
      after active stimulation vs respectively, 10.4 % and 5 % after placebo stimulation.

      However, predictive biomarkers of response are unknown, and cerebral metabolism may be a good
      candidate. It is admitted that the depressive state is correlated with specific modifications
      of glucose metabolism in circuits which are involved in the neurobiology of depression. The
      amplitude of these changes may correlate with clinical severity or may differ with treatment
      type, and cerebral metabolic changes might be an additional guide to treatment. Finally, the
      therapeutic effect might normalize cerebral functional activity and this might be an early
      correlate of clinical response. However the studies using functional imaging in a therapeutic
      approach or in the understanding of the physiopathology of the depression are not usable in a
      clinical practice of routine.

      The investigators suggest using a well-known analysis software (Scenium software, Siemens
      GmbH) who allows an automated analysis by the distribution of the cerebral metabolism by
      means of the F18-FDG TEP-TDM and a quantitative measure, expressed in regional consumption of
      glucose expressed by g / 100 g / min for every 18F-FDG TEP-TDM and for every region of
      interest. Image registering by the camera, remote of the injection of the tracer, lasts less
      than 10 minutes.The software also allows to compare the data acquired for a patient with a
      standardized database.

      The investigators will perform a opened study in two centers (Monaco Hospital/Nice CHU) on 50
      depressed patients aged from 40 to 65 years old, not having answered 2 lines of well led
      antidepressants. Low-frequency rTMS will be proposed in acute cure (3 in 6 weeks) in
      monotherapy followed by 6 months of rTMS for patients who have responded to acute treatment
      phase.

      Cerebral metabolic modifications (location and intensity) will be calculated after two
      PET-TDM in every patient, realized before and after the acute treatment by rTMS. We shall use
      the SCENIUM software which allows to compare each patient's data with a standardized
      database.

      At the end of the acute period of treatment, it will be proposed to patients who have
      responded to pursue rTMS treatment in a consolidation phase for 6 months. All patients will
      be longitudinally assessed during this consolidation period. One objective is to assess if
      initial TEP-TDM data and/or the amplitude of the induced metabolic variation is associated
      with the stability of the clinical answer in respondent patients
    

Intervention name(s): rTMS
Intervention type(s): Procedure
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: biological markers; rTMS