Anti Depressants

Rajat Srivastava GP Specialist Trainee, Psychiatry Leicester March 2008

• 1950s • 2 benzene rings + nitogen/oxygen ring • can be fatal in 5x therapeutic dose (QT

• <40 yrs, take cardiac history • >40yrs, baseline ECG

• inhibit re-uptake of 3 neurotransmitters
(anti-depressant effects)

• anti-cholinergic (dry mouth, blurred vision,
constipation, drowsiness, memory problems) hypotension, sexual dysfunction)

• adrenergic antagonism (postural

• 5HT2 antagonism (anxiolytic, reduced
sexual dysfunction, sedation) gain)

• Anti-histaminic (H1) (drowsiness, weight

TCAs : advantages
• well established efficacy & large literature • possibly more effective in severe

• low cost

• not first line due to side effect profile and
dangers of toxicity

• amitriptyline, dothiepin, doxepin,
imipramine, lofepramine

• first class of antidepressants to be used
clinically (1952)

• Iproniazid(derivative of isoniazid) found to

be ineffective in Rx Tuberculosis, but potent anti-depressant agent.

• 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 sumptomshyperphagia,hypersomnia) / anxiety disorders

• Risk of hypertensive crises (effect on • less with RIMAs, unless large load of
tyramine pressor amines) - hence foods high in tyramine to be avoided (cheese, meat extracts, alcohol, non-fresh fish & poultry


• isocarboxazid, moclobemide(RIMA),
phenelizine, tranylcypromine

• increased 5HT in the synaptic cleft • 5HT1 : antidepressant, anxiolytic, antiobsessive, anti-bulimic

• 5HT2 :agitation, akathisia, anxiety/panic,
insomnia,sexual dysfunction

• 5HT3 : nausea, GI upset, headache

SSRIs : 1st line
• relatively little affinity for dopamine, • relatively safe in overdose

histamine, alpha-adrenergic and cholinergic receptors : hence better side effect profile

SSRIs : problems
• contraindicated in manic episode & no
concomitant use with MAOIs insomnia

• commonly cause GI symptoms and • 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

• citalopram, escitalopram, fluoxetine,
paroxetine, sertraline
• • • •
The efficacy and safety of a new enteric-coated formulation of fluoxetine given once weekly during the continuation treatment of major depressive disorder. Schmidt ME; Fava M; Robinson JM; Judge R J Clin Psychiatry 2000 Nov;61(11):851-7.

• 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

NARIs (reboxitine)
• noradrenaline reuptake inhibition • novel mode of action • alerting effects useful in patiens with fatigue
or hypersomnia

SARIs (trazadone)
• serotonin antagonist and reuptake inhibitor • more sedating/anxiolytic, less sexual

• useful in depression with insomnia • but higher doses needed for antidepressant

NaSSA (mirtazapine)
• noradenergic & specific serotonergic • 5HT2 & 5HT3 antagonist (more sedating,
less GI SEs, weight gain) weight loss.

• used in depression with anxiety, insomnia, • used as an adjunct to SSRIs/SNRIs

choosing an AD : patient factors
• pregnancy : more data establishing safety of
older ADs(imipramine, amitryptyline). Fluoxetine the most studied SSRI major SE on infants)

• lactation : TCAs (most evidence), SSRIs(no •

heart disease
• MI : best avoided in the first 2 months.
SSRIs better than TCAs

• Arrhythmia : SSRI (not citalopram)

liver disease
• TCA : best evidence for imipramine • SSRI : some evidence for paroxetine. avoid

• MAOi :If necessary, use 30-50% dose

renal disease

• avoid venlafaxine and fluoxetine in severe

• TCAs lower seizure threshold • SSRIs first choice

adequate trial
• atleast 6 weeks of the highest tolerated
dose (upto BNF maximum) patients

• failure of adequate trial occurs in upto 25%

suicide risk
• risk of suicide may be increased in the early
stages of treatment

• patients with previous psychomotor
retardation most susceptible

Maintenance : First episode
• continue effective treatment for 6months 1year after remission

• gradual discontinuation • no evidence of benefit with indefinite

Maintenance : recurrent episodes
• if period b/w episodes <3yrs or severe
episodes(marked suicidal thoughts), treat for atleast 5 years (often indefinitely)