Depression and Treatment Pt 2 Flashcards
Ketamine was explored as a potential treatment for depression because:
1) other ADs have long lag times
- clinical effectiveness is directly related to adaptive changes primarily at the receptor level within DA/ NE/ and 5HT systems, which take time to change, hence the critical lag time.
2) many individuals do not respond to current antidepressants. rate of effectiveness has been suggested to be as low as 50-70%.
ketamine is a derivative of:
phenylcyclidine, a fast acting analgesic that exerts its effects by blocking glutaminergic NDMA receptors.
ketamine “street use”
dissociative anesthetic.
Ketamine has slow/rapid onset?
rapid onset, but also doesn’t last very long
Ketamine effects
- out of body experience
- dream like feeling
- hallucinations
- unusual thoughts
- blurred vision
- severe confusion
- dizziness
- drowsiness
- insomnia
- nausea
- vomiing
- extreme fear.
What dosage of ketamine is needed to see anti-depressant effects
a sub-anesthetic (dose that won’t make you pass out) IV dose has been found to affect depression. It is very quick acting to a typical antidepressant. It only lasts a few days though, it would require multiple injections if it were to be used as drug to help the individual with lag time.
In what settings is ketamine typically used for
it is not FDA approved. therefore it is only used in emergency situations in a hospital setting only for extreme depression treatment. has not been studied for long term safety and effectiveness
Kraus et al. 2017 did a literature review on ketamine. what were their 2 findings and conclusions
1) found that ketamine injections resulted in a reduction of depression on both the HAMILTON AND BECK scales
2) found that ketamine injections were far superior than placebo
- there was a response rate of 60-90%, which is higher than any other antidepressant treatment.
concluded: ketamine is a novel, rapid and efficaceous treatment options for pts suffering from treatment-RESISTANT depression, and exhibits rapid and significant anti-suicidal effects.
problems with ketamine
1) not fda approved thus little research thus long term effects are not known
2) high addiction rate because it can produce euphoric effects in non-depressed individuals
3) short term efficacy; if its gonna be used to off set the long lag time seen in normal antidepressants, ketamine would need to be injected every few days.
ketamine mechanism of action
- antagonist of the NMDA subtype of the glutamate receptor. because NMDA receptors are blocked, glutamate will bind to AMPAR’s instead, which facilitate the production and release of BDNF.
what is BDNF
a protein that is involved in the proliferation and differentiation and the survival of neuronal cells which contributes to the synaptic plasticity and connectivity of neural networks.
- BDNF levels are correlated to clinical efficacy.
- depression has been associated with decreased levels of BDNF, but BDNF levels increase after 3-4 weeks of antidepressant use, or after only 4 HOURS after ketamine administration.
depression has been associated with _____ levels of BDNF
depression has been associated with decreased levels of BDNF, but BDNF levels increase after 3-4 weeks of antidepressant use, or after only 4 HOURS after ketamine administration.
Outline the results of the Simon and Saravino experiment that compared pts who were prescribed antidepressants by general physicians, psychiatrists, or utilized individual psychotherapy (with no drug treatment)
- they compared the risk of suicide attempts/ possible suicide attempts in months prior-to and during treatment.
- the patterns in the TIMING of the suicide attempts was about the same for 3 group: there was an incidence of suicide attempts highest in the month before treatment -reflect the fact that these pts enter treatment at a time of crisis
- — this challenges the view that suicide is a side effect of anti-depressants after a pt’s ‘energy level’ increases as a consequence of treatment.
- the similarity in the pattern across all 3 groups suggest that this pattern reflects the expected course of improvement regardless of treatment.
- studies show that suicide is not a specific effect of any particular type of treatment
- this study also shows that suicide rate of pts of psychiatrists is higher than the suicide rates of physicians. It is often higher in psychiatrist groups because referrals to psychiatrists are typically higher risk pts.
the greater the baseline symptom severity, the __ the magnitude of difference favoring drug over placebo.
the greater the baseline symptom severity, the GREATER the magnitude of difference favouring drug over placebo.
- ie/ the greater the depression, the more likely you’ll see effects with the drug
side note: a limitation to this study is that it was a meta analysis which included only those in severe or very severe category: very few if any studies examine the effectiveness of antidepressants in pts with less severe depression.
Fournier et al (2010) studies showed what contradicting evidence to the antidepressant drug industry?
found that no effects of anti-deps were seen in mild, moderate and severe baseline (before treatment) symptoms. But significant and meaningful effects were seen in pts with very severe depression vs placebo.
they concluded that there is LITTLE EVIDENCE to suggest that the antidepressants produce specific pharmacological benefit for the majority of pts with less severe depression.
Andrews et al 2012 proposed that antidepressants may do more harm than good with their findings:
- found that antidepressants disrupt adaptive homeostatic mechanisms and causes disroder.
- 5HT regulates cell differentiation, temperature, blood clotting, digestion, insulin, cerebral blood flow (CBF), sexual behaviour and electrolyte balance. It is important that drugs do not “mess this system up”
- found that ADs may have limited efficacy: antidepressants are neither safe nor effective, they appear to do more harm than good.
in contrast to fournier and andrew’s studies that proposed that anti-depressants weren’t good, what did Cipriani A et al’s 2018 study propose? What issues were had with this study?
Cipriani et al seen that all antidepressants were more efficacious than placebo.
Issues;
1) vast majority of studies are funded by drug industry. it is really difficult to get negative results, or no results published. ex/ doing research and finding no difference is not interesting and won’t get published.
2) novelty bias: antidepressants seem to perform better when they are newly released, but lose efficacy as time goes on
3) statistical vs clinical significance: while rseults may be statistically significant, the effect sizes are modest at best.
