L 6+7 - Antidepressants Flashcards
What are antidepressants used for?
- treat major depression
- depressive phase in Bipolar
- depressive episode in schizophrenia
- preventing relapse
- adjunct treatment to anxiety disorders, OCD.
- adjunctive treatment for eating disorders
sometimes… for night sedation.
efficacy of antidepressants?
all pretty similar… 50-60% improvement
placebo is 30-40%
What affacts efficacy of antidepressant?
Prior treatment history in
patient/family members
Patient preferences
Expertise of prescribing provider
Side effect profile(sedating or activating)
Safety in overdose (10-15 days of a TCA can be a lethal overdose)
Drug-drug interactions
What are some therapeutic targets/mechanisms of actions in antidepressants
- blocking monoamine reuptake
- block a2 receptor and therefore increase release of NA by blocking presynaptic autoreceptor
- block enzyme monoamine oxidase (MAO inibitor)
some have multiple actions.
(serotonin is a monoamine)
Do antidepressants help healthy humans?
no it does not elevate mood in healthy people
What are the different classes of antidepressants available?
- Tricyclic
- MAO inhibitors
- SSRIs
- SNRIs (dual serotonin and NA)
- serotonin modulators and stimulators
- serotonin-2 antagonist and reuptake inhibitors (SARIs)
- NRI (specific NA reuptake inhibitors)
- NDRA (NA + DA reuptake inihib)
- NaSSAs (NA and 5-HT antag)
- Serotonin reuptake enhancer
- atypical antipsychotics
- other .. like ketamine..
- atypibuspirone, lithium, thyroxine
three generation of antidepressants that we use?
- 1st gen - MAOIs and tricyclics
- 2nd gen - SSRIs
- 3rd gen - Tricyclic with a twist
What are 1st gen antidepressants?
MAO inhibitors!
Mao inhibitors?
- inhibitor the action of monoamine oxidase, which breaks down dopamine, NA and serotonin.
= mORE NT!
side effect = blocks MAO in the liver, builds up tyramine, high BP and increased risk of stroke.
TCAs? How do they work?
Tricyclic antidepressants - blocks the reuptake of NA and serotonin, therefore increase NT in synapse.
- at least 3 other modes of action - blocking other receptors gives rise to side effects
what are the side effects associated with TCA’s, that are related to certain receptor blockades?
Block muscarinic cholinergic receptors - producing dry mouth, blurred vision, urinary retention, constipation and memory problems
Block H1 histamine receptors - causing sedation and weight gain
Block α1 adrenergic receptors - causing postural hypotension and dizziness
What are some generalised side effects of TCAs?
- increased freq of epileptic seizures.
- sedation
- cardiotoxicity.
2nd gen antidepressants?
SSRIs!
they block the reuptake of serotonin only.
What is the mech of action for SSRIs?
specifically blocks the reuptake of serotonin, without affecting other NTs.
Side effects: nausea, sexual dysfunction (serotonin receptors also in gut, hypothalamus and sex organs)
Little cardiovascular concern
Side effect of SSRI?
Common:
Stimulant effects such as ‘nervousness’, insomnia
Other CNS effects: dizziness, headache, tremor
GI effects: nausea, vomiting, diarrhoea, abdominal discomfort
Weight loss/gain
Uncommon:
Sedation; dry mouth; sweating; sexual dysfunction including decreased libido, anorgasmia, delayed ejaculation
Rare:
Mania; convulsions; movement disorders: tremor, akathisia, dystonia or dyskinesia
ECG, BP or heart rate changes (arrhythmias)
SSRIs vs Tricyclics?
- SSRIs are more selective with serotonon… less anticholinergic effects
- SRRIS free from membrane stabilising effects on the heart, therefore does not affect cardiac risk
but
not more effective
action is not faster.
but less side effects :)
less sedation, anticholinergic effects, cardiotoxicity and weight gain.
BUT more gastro effects
What to prescribe if suicide risk is high
better to prescribe SSRI than TCA. easier tolerated.
3rd gen antidepressant
“tricyclics with a twist”
- they do a rang eof things… SSRI+ almost..
- acts as an SSRI but also antagonises 5-ht2 and 5-ht3 receptors…therefore restricting action to only 5-ht1 receptor
- efexor (venlafaxine; SNRI), mitazapine
Venlafaxine?
aka Efexor
- does bOTH what SSRI and TCAs do
**Selectively inhibits reuptake of serotonin and NA (and, to lesser extent, dopamine)
**Shares similar advantages with the SSRIs over tricyclics
potential advantages over SSRIs.
Advantages of venlafaxine over ssri?
- increase in efficacy at higher doses, due to addition of second action on NA.
- effect is 50% higher than SSRIs.
- more rapid onset of action (1 week)
- safe at high dosage
- less interactions with other drugs.
Disadvantages of venlafaxine, when compared to SSRI?
potential for blood pressure elevation at higher doses - requires BP to be monitored closely during first 2 months of being stabilised on any dose above 225 mg/day
Original need for twice a day dosing schedule now overcome with extended release formulation
dose needs to be titrated
Side effects of venlafaxine/efexor?
Most common side effects: nausea
dizziness sedation
At higher doses, dose-dependent increases in:
blood pressure (rarely observed below 225 mg/day) sweating
tremors
Bupropion
- aka zyban also used for smoking cessation
- bLOCKS REUPTAKE of DOPAMINE and/or NA.
- very weak effect on serotonin, if at all.
- decreased level of side effects in depression
- not much of an effect on anxiety
Which classes of antidepressant have sedative effect?
tricyclic and SSRIs.. some
Classes of symptom in depression?
- physical - appetite, sleep
- cognitive and behavioural
What kind of symptoms is best alleviated by antideprssants?
physical ones - sleep disturbance, appetite.
What helps most with . cognitive and behavioural problems ?
CBT… psych strategies
What is the usual course of recovery in depression
appetite and sleep improve first
then behaviour second
thoughts and feelings last.
What is the difference in presentation for someone with DA dysfunction and someone with 5-HT dysfunction?
DA dysfunction = REDUCED POSITIVE AFFECT
- loss of happiness, anhedonia, fatigue, decreased alertness, decreased self confidence
5-HT dysfunction = INCREASED NEGATIVE AFFECT
-depressed mood, guilt, disgust, anxiety, hospility, irritability, loneliness
NA dysfunction is in between both of these… can swing eac way but not as severe.
What NT systems would you modify for fatigue and concentration problems?
NA and DA.
so use... NDRI, NRI SNRI MAOI stimulants
what NT systems would you modify for sleep problemms
5-HT and GABA and histamine systems
hyponotics
sedating antidepressants - mirtazapine
Usually, with antidepressants, what is the course of recovery …
therapeutic effects are slow.. then quickly go up to plateu.
side effects more quickly commence… then decrease over time…
What are the first line monotherapies for depression then?
SSRI NDRI SNRI SDA BP BP - lamotrigine (antipsychotic/anticonvulsant)
What age range do antidepressants work best for
26-64 - adults
Placebo role in antidepressants?
HUGE ROLE…. 20-25% of the effect for antidepressants…
50% natural cause of illness
then 20-25% is down to the actual antiderpssant
When a meta analysis was run.. what was found for the effect of SSRIs?
- did not meet 3 point drug-placebo criterion for clinical significance.
- improvement was a function of baseline severity. those those at the tail ends improved least, those in the middle had the largest gains.
drug type didnt mediate this effect.
Why might some studies find a greater effect for antidepressant in extremely severe patients?
because the placebo effect is less in those severely depressed
(this is when looking at drug vs placebo effect)
efficacy of psychotherapy vs combined with medication?
Mean effect size for the difference between PT and
combined therapy was 0.35
Differences between PT and combined was smaller in those studies that employed CBT
At follow up at 3, 6 and 12 mths; no difference between PT and combined
Conclusion: Combined therapy is more effective than PT treatment alone, but it is not clear whether this difference is relevant from a clinical perspective
key principles for using antidepressants?
Use antidepressants, not minor tranquilizers /
benzodiazepines
Use adequate doses for an adequate amount of time
Start slow and work with side effects but titrate to an effective dose as needed
Change medication if not effective
Usually after 8-10 weeks
how long should you wait until you say a medication is not working (antidepressant)
usually 8-10 weeks.
change medication
How should we education patients on antidepressants
Key messages
How do these medications work?
By restoring a chemical imbalance in the brain
There are several options (over 20 available medications)
Anticipate
Patient concerns about medications Side effects (these can be managed) Problems with adherence
Reinforce
Need for continuation or maintenance treatment to prevent relapse even after the patient feels better
What happens if they dont respond to SSRI
about one in four patients who are changed to either another SSRI, Buproprion-SR, or Venlafaxine XR will respond to the new drug
27–32 % of patients will respond to augmentation with Buspirone or Buproprion
How to manage side effects?
Short term strategies
Wait and support (e.g., GI side effects)
Adjust medication timing (e.g., take sedating meds at bedtime)
Consider temporary dose reduction
Treat side effects (see intervention manual)
Change to a different antidepressant
Change to or add psychotherapy
When to stop antidepressants?
Treat all adults for 4-9 months after initial response.
Treat those at high risk for relapse for 2 years or longer. Some
may need lifetime treatment.
Maintenance treatment should be at full dose.
Make a relapse prevention plan.
Taper antidepressants slowly to avoid discontinuation syndrome.
What are the guidelines for treatment with moderate depression
all antidepressants, CBT & IPT equally effective
What are the guideless for treatment of severe depression
all antidepressants, psychotherapy later.
What are the guidelines for severe depression with psychosis
ECT alone or TCA plus antipsychotic is superior to TCA alone.
What are the long term effecst when you compare antidepressant and Cog therapy
prior treatment with CT protected against relapse of depression at least as well as continued provision of ADM and better than ADM treatment that was subsequently discontinued.
more people relapse with discontinue medication, than those who discontinue cognitive therapy…. CT has more enduring effect
While acute changes with the either CT or ADM might be due to a similar mechanism, CT can be assumed to also produce changes that ADM does not.
neurological explanation for why cog therapy is more beneficial and enduring than medication?
Acutely depressed individuals are characterised by decreased prefrontal function possibly arising from increased amygdala reactivity
CT operates by increasing prefrontal function, while ADM operates more directly on the amygdala
These treatments might thus result in end states that are, in one important respect, similar: normalised amygdala and PFC activity in the short term
If the amygdala is the “point of entry” for environmental stressors, cessation of ADM could leave the person at risk of having strong maladaptive reactions to new environmental insults
By contrast, CT works by building the skills that require active operation of PFC, thus making the effects more enduring
