Antidepressants And Treatment Of Bipolar Disorder Flashcards
Cyproheptadine
Serotonin (5-HT2) antagonist used in emergency maintenance of serotonin syndrome
Side effects: “Atropine-like” side effects - sedation - blurred vision - orthostatic hypotension - urinary retention - tachycardia
5-HT(2) receptor modulators
Trazodone, Nefazodone
Atypical antidepressant:
5-HT(2a), a(1) and H(1) antagonists
- also blocks SERT receptors
Indications:
- major depression (MDD)
- very good with MDD + insomnia patients, but not 1st line due to ADRs*
- anxiety
- hypnotic agent (most common prescribed reason for trazodone)
ADRs:
- extreme sedation
- nausea
- orthostatic hypotension (trazadone only)
- priapism (trazadone only)
- hepatotoxicity (Nefazodone only)
Contraindications:
- liver failure/disease (Nefazodone only)
- use with MAOIs (ALL)
5-HT receptor modulators
Vilazodone and vortioxetine
Atypical antidepressant:
5-HT reputable inhibitors (SERT)
5-HT(1a) agonists (vortioxetine > vilazodone)
5-HT(3a) antagonists (vortioxetine only)
Indications:
- MDD
- anxiety
ADRs:
- weight gain (vilazodone only)
- sleep disturbances (vortioxetine only)
- sexual dysfunction (vortioxetine only)
- nausea
- anticholinergic effects
- *serotonin syndrome (if combined with other serotonergic drugs)
Contraindications:
- use with MAOIs (BOTH)
Mirtazapine
Atypical antidepressant
- 5-HT(2/3a) antagonist
- H1- antagonist
- a2 antagonist
Indications
- refractory MDD
- first line in patients with insomnia and MDD due to more favorable ADR profile*
ADRs:
- extreme sedation
- increased appetite and weight gain (most reported)
- reduced nausea and vomiting
- dry mouth
- somnolence
- Very rare agranulocytosis (more rare than clozapine)
Bupropion
Blocks NET and DAT
(NE and dopamine reuptake receptors)
- increases levels of NE and dopamine in presynaptic cleft
- *also blocks nicotinic receptors
Indications:
- MDD
- prophylaxis for seasonal depressive disorder
- smoking cessation*
- ADHD
- neuropathic pain and weight loss (off-label)
ADRs:
- anxiety
- mild tachycardia
- HTN
- irritability
- tremors
- anticholinergic effects
- *increases odds of seizures (especially in bulemic/ anorexia patients)
Contraindications:
- patients who have seizures and general bulimic or anorexia patients (regardless of whether they have had seizures or not)
while not contraindicated, should use hesitantly with SSRIs due to possible DDIs
MDD epidemiology
17% lifetime prevalence in the US
- women are more likely, but not by much
- increases risk of coronary artery disease, diabetes and stroke
MDD decreases quality of life and prognosis of another illness if both are present
Antidepressant possible indications
MDD
Panic disorder
Generalized anxiety disorder
PTSD
Obsessive-compulsive disorder
Neuropathic pain
Fibromyalgia
Urinary symptoms
General principles of treatment with antidepressants
before beginning therapy, rule out drug induced or medical causes of depression.
most antidepressants have similar efficacy, therefore patient factors and ADR profile is generally what is looked at for treatment choice
Goals of treatment: (remission)
1) acute phase
- resolution of current symptoms
- 6-12 weeks
2) continuation phase (prevent relapse)
- elimination of residual symptoms
- 4-9 months
3) maintenance phase (prevent recurrence)
- stopping another depressive episode
- 12-36 months
- may be lifetime
What is the #1 risk with taking antidepressants?
All antidepressants carry increased risk of suicidal behavior
- especially in adolescences
Generally, what antidepressants are used the most?
SSRIs and SNRIs
Mirtazapine
Bupropion
Monoamine hypothesis
Is a hypothesis associated behind the pathophysiology behind MDD
A deficiency in monoamine signaling in the cortical-limbic regions
- reserpine use in antipsychotic cases causes depression as a symptom (reserpine depletes monoamine neurotransmitters)
- antidepressants increases levels of monoamines
Glutamatergic hypothesis
Is a hypothesis associated behind the pathophysiology behind MDD
A deficiency in glutamine signaling in the cortical-limbic regions
- esketamine (NMDAR antagonist) is very good at treating depression (bad ADRs thou)
How long does it usually take for antidepressant action to take place?
Full antidepressant effects usually take 4-6 weeks or longer.
This often caused due to paradoxical mechanisms involving autoreceptors
- 5-HT(1a/b) and a2-adrenergic
- treatment acutely ACTIVATES these autoreceptors, reducing levels of these amines
- *hypothesized to potentially be the cause of increased suicidal ideology when on antidepressants
chronic treatment down regulates inhibitory autoreceptors (due to habituation), so as long as the patient can adhere, the treatment usually works after 6 weeks
General differences between typical and antidepressants
Typical
- increase monoamine levels by inhibiting uptake or degradation of monoamines
Atypical
- increase monoamine levels by either inhibiting reuptake of monoamines or targeting the receptors themselves as agonists/antagonists
SSRIs
Fluoxetine, fluvoxamine, paroxetine, sertraline, escitalopram, citalopram
Target only the SERT receptors
- causes excessive stimulation of 5-HT receptors
Take 4-8 weeks usually to show improvement
Become prominent in the 1980s and are now the first line therapy for MDD
Relatively tolerable and cost is low. Also PO and either daily or weekly (fluoxetine only)
Indications:
- anxiety
- PTSD
- OCD
- panic
- PMDD
- bulimia
- Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) (super rare)
common ADRs:
- anxiety/nervousness
- insomnia
- nausea
- serotonin syndrome (high levels of coadministration with other serotonergic drugs)
- sexual dysfunction/decreased libido
- emesis
SSRI-specifically ADRs
QT prolongation = citalopram
Anorexia = fluoxetine
Somnolence = fluvoxamine
Anticholinergic effects = paroxetine
Serotonin syndrome
A life-threatening ADR associated with overload of serotonin
Symptoms
- hyperthermia
- hyperreflexia*
- generalized muscle rigidity*
- myoclonus
- tremors
- autonomic instability (sweating/hyperthermia/increases HR/BP/mydriasis*)
- irritability
- agitation
- coma and death (if not treated)
- respiratory failure (if taken with alcohol or benzos)
- usually occur only in coadminstration of other serotonergic drugs or if taking CYP2D6/ 3A4 inhibitors*
How to tell serotonin syndrome from NMS based on symptoms?
SS = hyperreflexia, mydriasis, generalized muscle rigidity
NMS = hyporeflexia, normal pupils, “lead pipe rigidity” (legs and arms specific)
