Finale
MDD-- Monoamine hypothesis of depression, prescribing considerations- the theory is that
depression is caused by a deficiency in monoamine neurotransmission. And mania is the
opposite - due to an excess of monoamine neurotransmission.
This hasn't really been proven yet, so then the focus shifted to the monoamine receptor
hypothesis - that the abnormality of receptors for monoamine NTs cause depression. In that
case, the lack of NT causes upregulation of receptors.
Also not proven yet. Right now the focus is on regulation of gene expression, growth factors,
environmental factors, and epigenetic changes.
Prescribing considerations
- do not give antidepressants as monotherapy for bipolar - always combine with mood
stabilizer. Must rule out mania or hypomania so don't confuse MDD with BPD and induce
mania.
Monitor infant irritability when prescribe SNRI for breastfeeding.
Also keep in mind: client preference, prior treatment response, anticipated adverse effects,
comorbidities, half life and interactions (if they will forget to take med, choose something longer
acting), cost.
Start patient on drug for 4-8 weeks, on lowest recommended dose. If doesn't work, first
increase dose, then switch to diff drug in same class and give adequate trial of high enough
dose, then switch to a drug in a different class, then add a second med.
For older people - citalopram and escitalopram should be ½ dose, avoid paroxetine if have
history of falls, avoid TCAs prescribed with out CNS depressants.
SSRIs what screens should be completed prior to prescribing a SSRI?
- for SNRIs need to check BP before and during treatment.
Which age group is most at risk when prescribed a SSRI? Why? Kids and adults under 25 -
increased risk of suicide
Which SSRI has the least CYP interactions -
escitalopram (Lexapro).
Good for forgetful people -
fluoxetine (has 2-3 day half life). Also sertraline (27-36 hour ½ life).
Longest acting
fluoxetine has the longest half life 1-2 weeks. When adding or switching antidepressants use
caution for 5 weeks after stopping fluoxetine
More likely to cause discontinuation syndrome. -
paroxetine
Safe in nursing and pregnancy and breastfeeding
sertraline
Contraindicated in pregnancy
paroxetine (risk of atrial septal defect).
Which medications are used as adjuncts?
, Buproprion,
Lowest risk of sexual side effects
buproprion, mirtazapine
What is serotonin syndrome
When use two serotonergic drugs together. Symptoms: mental status changes (agitation,
hallucinations, delirium, coma), autonomic instability (tachycardia, dizziness, diaphoresis,
hyperthermia), neuromuscular symptoms (tremor, rigidity, myoclonus, hyperreflexia,
incoordination), seizures, and/or gastrointestinal symptoms (nausea, vomiting, diarrhea).
Treatment - stop med, supportive care, benzos.
MAOIs black box warning
Suicidal ideation in children, adolescents and young adults
MAOI half life
2-4 hours
SSRIs black box warning
suicidal tendencies
MAOIs (monoamine oxidase inhibitors)
Antidepresents durgs that inhibit the enzyme that deatctiviates dopamine, norepiniphrine, and
serotonin. MAOIs appear to be most effective for treating non-endogenous and atypical
depressions.
Side-effects include anticholnergic effects, insomnia, agitation, confusion, and wieght gain.
when taken in conjuction with other drugs or foods containing tyramine, they can cause a
hypertensive crisis.
Lithium levels can be increased by nonsteroidal anti-inflammatory
drugs (NSAIDs) and angiotensin-converting enzyme (ACE) inhibitors
and decreased by caffeine and mania.
Role of L-Methylfolate in depression treatment
is necessary for the synthesis of monoamines. We generally get l-methylfolate from dietary folic
acid, but about 50% of people are deficient. There are small studies that say that supplementing
l-methylfolate or regular OTC folate may help as adjunctive treatment of depression.
Recommended to try the OTC folate first. Role of L-Methylfolate in depression tx
Suboptimal folate levels in depressed patients (adjunct to antidepressant)
• L-Methylfolate is a bioavailable form of folate
• L-methylfolate, or 6-(S)-5-methyl-tetrahydrofolate, is derived from folate and is the form that
enters the brain and works directly as a methyl donor and monoamine synthesis modulator
Why is L-Methylfolate recommended as an adjunct in depression?
Treatment with l-methylfolate seems to be safe, has few if any side effects, and is generally
less expensive than augmenting with a second branded antidepressant or atypical antipsychotic
Pregnancy
Paroxetine is contraindicated in pregnancy due to the risk of congenital
defects, including atrial septal defects.