Anti Depressants
Rajat Srivastava
GP Specialist Trainee, Psychiatry
Leicester
March 2008
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Very Useful and practical guide to understand mechanisms and pharmacokinetics and pharmacodynamics of antidepressants
Typology: Lecture notes
2018/2019
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Anti Depressants
Rajat Srivastava GP Specialist Trainee, Psychiatry Leicester March 2008
TCAs
1950s
2 benzene rings + nitogen/oxygen ring
can be fatal in 5x therapeutic dose (QT prolongation)
<40 yrs, take cardiac history
40yrs, baseline ECG
TCAs
inhibit re-uptake of 3 neurotransmitters (anti-depressant effects)
anti-cholinergic (dry mouth, blurred vision, constipation, drowsiness, memory problems)
adrenergic antagonism (postural hypotension, sexual dysfunction)
TCAs : advantages
well established efficacy & large literature
possibly more effective in severe depression
low cost
TCAs
not first line due to side effect profile and dangers of toxicity
amitriptyline, dothiepin, doxepin, imipramine, lofepramine
MAOIs & RIMAs
MAOIs : irreversible inhibition of MAO-A & MAO-B, leading to accumulation of monoamines in synaptic cleft
RIMAs : reversible inhibition of MAO-A
MAOIs / RIMAs :
Indications
2nd line for treatment resistant depression (particularly atypical sumptoms- hyperphagia,hypersomnia) / anxiety disorders
MAOIs / RIMAs
isocarboxazid, moclobemide(RIMA), phenelizine, tranylcypromine
SSRIs
increased 5HT in the synaptic cleft
5HT1 : antidepressant, anxiolytic, anti- obsessive, anti-bulimic
5HT2 :agitation, akathisia, anxiety/panic, insomnia,sexual dysfunction
5HT3 : nausea, GI upset, headache
SSRIs : problems
contraindicated in manic episode & no concomitant use with MAOIs
commonly cause GI symptoms and insomnia
maybe less effective for severe depression
problems on discontinuation (SSRI withdrawl syndrome)
SSRIs & sexual
dysfunction
seen in upto 50% of patiens
reduced libido in men and women
anorgasmia in women
increased ejaculation latency
Rx : reduce dose, sildenafil, switch
TeCAs
less anticholinergic side effects
mianserin and maprotiline
SNRIs
(venlafaxine)
seretonin & noradrenaline
possibly most rapid onset of action
available in controlled release form
need to monitor BP if dose >200mg