Table 2.
Study protocol
| Authors | Objective | Treatment | Protocol timing | Antidepressant response | Responders to treatment | Main findings |
|---|---|---|---|---|---|---|
| Bernier D 200918 | To evaluate neurochemical correlates of sleep restriction | Partial SD | 1H-MRS on the baseline day and the postsleep restriction day | Improvement in HDI total score and at least a 30% improvement in HDI mood score | 5 out of 11 | “Baseline pontine Cho levels distinguished subsequent responders from nonresponders; SD caused a 20.1% decrease in pontine tCr and 11.3% increase in prefrontal Cho in both groups, MDD and healthy controls” |
| Block W 200917 | To study metabolic changes to identify correlates and predictors of treatment response | SSRI (5 citalopram) TCAs (6 nortriptyline) | 1H-MRS at baseline and after 8 weeks | – | Significant decrease in BDI score | “Significant reduction of Glx/Cr and Gln/Cr in the patient group; Gln/Glx ratio showed a trend towards significant reduction; individual effect of treatment correlated with an increase in the NAA and Cho absolute concentrations; low baseline NAA and Cho levels predicted positive treatment effects; no difference in any clinical or metabolic measure, either at baseline or at follow-up between the two treatment groups” |
| Murck H 200916 | To address whether Glx and Gln level changes are related to clinical improvement | Total SD | 1H-MRS pre and post 24h of total SD | – | Significant decrease in HAMD score | “TSD led to an increase in Glx and Gln in the DLPFC only of male patients; Gln increase in patients with vegetative melanchonia; no change in POC” |
| Luborzewski A 200715 | To evaluate neurochemical brain alterations before and after 10 days of high-frequency rTMS of the left DLPFC | 10 sessions (2 weeks) of rTMS of the left DLPFC in naive subjects | 1H-MRS carried out before and after 10 days of rTMS | – | 6 out of 17 | “In the DLPFC, lower Glu and Cho in responders before treatment; after TMS,mean individual Glu increased in responders and decreased in non-responders; Cho increased significantly in responders. No neurochemical alterations in the ACC were detected after rTMS” |
| Gonul AS 200614 | To test the effect of antidepressant treatment on metabolite levels in the left medial frontal cortex | 7 with SSRIs (4 fluoxetine; 3 paroxetine),13 with SNRI (venlafaxine) | 1H-MRS at baseline and after response to treatment | ≥50% decrement of HAMD initial score | 70% (14) | “Pre-treatment NAA/Cr values lower than those of healthy subjects; MDD treatment has significant effect on NAA/Cr; after therapy NAA/Cr values increased significantly in responders (14/20)” |
| Sanacora G 200613 | To test the effect of CBT on occipital cortex GABA vs SSRIs and ECT | CBT | Pre and post 12-week course of CBT | – | Significant decrease in HAMD score | “Clinical response not correlated with pre-CBT GABA levels or post-CBT GABA change; CBT shows a different effect on occipital GABA compared to ECT and SSRI” |
| Michael N 200312 | To evaluate neurotrophic changes during ECT in the left amygdala region | ECT | Pre and post ECT monotherapy;non responders underwent a third 1H-MRS after finally responding to combined ECT/pharmacotherapy | >60% reduction of MADRS baseline score | 10 out of 13 | “Significant Glx trend towards a reduction in patients with unipolar depression; successful ECT was accompanied by increased NAA and Glx levels compared to baseline in all patients; similar increase in NAA was observed in 5/14 non-responders after they had finally responded to the combined ECT/pharmacotherapy” |
| Michael N 200311 | To evaluate metabolic DLPFC changes before and after ECT | ECT | 2–3 ECT × week; 4/12with an insufficient response re-evaluated after a ECT + pharmacotherapy | >60% reduction of MADRS baseline score | 8 out of 12 | “Responders (8/12) showed a marked Glx increase, no longer different from that of controls; it correlated with improvement of MADRS scores; a third measurement revealed a Glx increase after recovery in 2/4 non-responders; Glx was significantly reduced (approximately 67%) prior to ECT in all patients” |
| Obergriesser T 200310 | Follow up of the quantitative changes in Cho and NAA signals in the hippocampal region of patients who remitted from MDD after a course of ECT | ECT | Patients previously studied with 1H-MRS pre- and post-ECT were re-evaluated after a mean of 20±8.6 months after the last ECT | – | 10 out of 12 | “No changes in hippocampal NAA signal; the initially significant increase in the Cho signal reversed to values close to pre-ECT levels” |
| Pfleiderer B 20039 | To evaluate the effects of succesful ECT on Glx levels in the anterior cingulum | ECT | 1H-MRS within 24–48 h of the effective ECT (responders) or after the last ECT (non responders) | >60% reduction of MADRS baseline score | 10 out of 17 | “Marked increase of Glx in responders compared to baseline levels, no longer different from those of controls; stable Glx levels after remission; ECT non-responders did not show marked Glx increase but after clinical response to ECT/venlaflaxine revealed a twofold Glx increase” |
| Sanacora G 20038 | To evaluate occipital cortex GABA increase after ECT | ECT (7/8 bilateral) | Before and at least 1 day after completion of final ECT session | – | “25% complete; 62.5% partial; 12.5% no” response | “Post-ECT GABA significantly increased and higher than pre-ECT concentration (7/8 pts); in 4/8 more than 85% over their pre-ECT levels; still no significant correlation between GABA change and clinical response” |
| Sanacora G 20027 | To evaluate alteration of occipital cortex GABA after SSRI | SSRIs (8 fluoxetine, 3 citalopram) | 1H-MRS before and after a minimum of 5 weeks of SSRI | – | 7 out of 11 had >50% reduction in HAMD score | “Occipital cortex GABA significantly higher after treatment (9/11); no significant correlation between pretreatment and change in occipital cortex GABA and clinical improvement” |
| Ende G 20006 | “Monitoring of quantitative changes in the NAA and Cho signals in the hippocampal region” | ECT | At least 2 datasets were acquired from each patient: one before ECT started and a second after 5 or more ECT treatments, within 30 hours to 10 days of ECT | – | “All patients showed clinical amelioration of depression after ECT (>50% reduction in HAM-D score)” | “No changes in the hippocampal NAA signal after ECT; significant mean increase of Cho-containing compounds” |
| Sonawalla SB 19995 | To assess the relationship between true drug response to fluoxetine and Cho/Cr in the basal ganglia | SSRI (fluoxetine) | Patients underwent 1H-MRS before and after an 8-week open trial with fluoxetine | Improvement on CGI | 8 out of 15 | “Statistically significant difference in Cho/Cr from baseline to week 8between true drug response group (increased by 20%) and placebo pattern response/non-response group (decreased by 12%); no significantly different change in NAA/Cr after 8 weeks of treatment” |
| Charles HC 19944 | To test Cho in basal ganglia and thalamus before and after recovery | SARI (nefazodone) | 1H-MRS before and 2–3 months after therapy commenced | – | – | “Cho/Cr pre-therapy levels were elevated (compared to those of normal subjects); they fell significantly from pre to post-therapy (reaching control levels)” |
Abbreviations: NAA=N-acetylaspartate; Cr=creatine; tCr=creatine-plus-phosphocreatine; Cho=choline-containing compound; Glu=glutamate; Glx=glutamate and glutamine; GABA=γ-aminobutyric acid; ACC=anterior cingulate cortex; DLPFC=left dorsolateral prefrontal cortex; POC=parieto-occipital cortex; SARIs=serotonin antagonist reuptake inhibitors; SNRIs=serotonin norepinephrine re-uptake inhibitors; SSRIs=serotonin reuptake inhibitors; TCAs=triclyclic antidepressants; ECT=electroconvulsive therapy; CBT=cognitive behavioural therapy; rTMS=repetitive transcranial magnetic stimulation; SD=sleep deprivation; MDD=major depressive disorder; DS=discontinuation syndrome; HAMD=Hamilton depression rating scale; HDI=Hamilton Depression Inventory; MADRS=Montgomery Asberg Depression Rating Scale; CGI=Clinical Global Impression.