Treating Depression in the General Population Flashcards
antidepressants
antidepressants (i.e., selective serotonin-reuptake inhibitors) the overwhelming treatment for depression
how antidepressants work
affect certain brain circuits and the chemicals (neurotransmitters) that pass signals along neurons in the brain
neurotransmitters
- > serotonin
- > dopamine
- > norepinephrine
reuptake inhibitors
process in which neurotransmitters are naturally absorbed back into the nerve cells in the brain
reuptake inhibitors prevents this, and the neurotransmitter stays at least temporarily in the gap between nerves (synapse)
how are reuptake inhibitors benefical?
keeping levels of the neurotransmitters higher could improve communication between nerve cells, and can strengthen circuits to the brain which can regulate mood
front line antidepressants
- > prozac
- > zoloft
- > celexa
- > lexapro
initial severity and antidepressant benefits, meta-analysis (kirsch et al.)
to establish the relation of baseline severity and antidepressant efficacy using a relevant dataset of published and unpublished clinical trials
drug vs placebo differences in Hamilton Rating Scale of Depression (HRSD)
results of initial severity and antidepressant benefits
- > weighted mean improvements was 9.60 points on the (HRSD) in the drug group and 7.8 in the placebo group
- > yielding a mean drug-placebo difference of 1.80 on the HRSD improvement scores
- > fails to meet the three-point drug-placebo criterion for clinical significance used by National Institute for Health and Care Excellence (NICE)
- > standardized mean difference (d), mean change for drug groups was 1.24 and 0.92 for placebo both very large magnitudes
- > the difference between improvement in the drug and placebo group was 0.32, falls below the 0.5 standardized mean difference criterion that NICE suggested
clinical significant difference of severity, drug and placebo
2 bell curve graphs put into each other to see the mean difference between the groups (treatment vs placebo)
- > effect size
- > % of treatment group mean difference above control group mean
- > when an effect is 0, the distribution of the scores of the 2 groups overlaps completely and the midpoints are the same (50% of participants’ scores on either side of the mean)
- > as effect size becomes larger there is a net gain so that a greater percentage of the participants’ scores in one group
- > an effect of 0.3 suggests that the treatment group has a net gain of 12% over the control group / that is the score of the average person in the treatment group exceeds the scores of 62% of the control group
conclusion of initial severity vs antidepressant benefits
- > drug-placebo differences increased as a function of initial severity, rising from no difference at moderate levels of initial depression to relatively small difference for patients with very severe depression
- > reaching conventional criteria for clinical significance only for patients at the upper end of the very severe depression category
- > the relationship between initial severity and antidepressant efficacy could be from decreased responsiveness to placebo among very severely depressed patients, rather than a benefical effect from medication
- > the drugs used to treat depression are effective, but for most people, its the placebo effect that makes people feel better, instead of the active ingredient
21 antidepressant drugs for the acute treatment of adults with major depressive disorder meta analysis (Cipriani study)
- > all antidepressants were more efficacious than placebo in adults with MDD (major depressive disorder)
- > however, the placebo was favored from the dropout rate from the drug the participants were taking because they thought it wasnt working
- > lingering questions: is it because of the active ingredient in the drug or that the placebo stops working as effectively?
- > all-cause attrition is only a crude proxy for tolerability can not determine the benefits and harms, especially harms that matter most to patients
questionable drug approval protocol
- > to approve any drug, the Food and Drug Administration only requires companies to show their drug is more effective than a placebo in only 2 clinical trials - even if many other trials failed
- > implications: the FDA for antidepressants has a fairly low bar. A drug can be no better than placebo in 10 trials, but if 2 trials show it to be better, it gets approved
why are we prescribing antidepressants so agressively?
- > how doctors are trained: front line treatment often involves medication instead of other methods such as exercise to lower blood pressure compared to a medication to lower blood pressure
- > big pharma
- too much money involved in development and sales
- billions of dollars
psycho-therapy or “talk therapy”
- > the role of psychotherapy in treating clinical depression is to help the person develop good coping strategies for dealing with everyday stressors
- > additionally, it can encourage to use medications properly
interpersonal therapy
- > events surrounding interpersonal relationships do not cause depression
- > depression occurs within an interpersonal context and affects relationships and the roles of people within those relationships
- > by addressing interpersonal issues, interpersonal therapy for depression by improving interpersonal relationships with others (family and friends) could benefit the depressed
ketamine and depression
- > ketamine is a fast-acting anesthetic and painkiller, can produce vivid dreams and a feeling of mind-body separation and has anti-depressant properties
- > triggers gluamate production as a result makes brain form new neural connections in the cortex
- > this makes the brain more adaptable and able to create new pathways giving patients the opportunity to develop more positive thoughts and behaviors
- > approved at march 2019 from the possibility of effectiveness
- > panel A, efficacy of ketamine vs others like (placebo) ketamine is favored more
- > panel B, efficacy of ketamine with ECT is slightly favored
