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

• 5HT2 antagonism (anxiolytic, reduced

sexual dysfunction, sedation)
• Anti-histaminic (H1) (drowsiness, weight
gain)
 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

• 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 & 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 : SEs

• Risk of hypertensive crises (effect on

pressor amines) - hence foods high in
tyramine to be avoided (cheese, meat
extracts, alcohol, non-fresh fish & poultry
• less with RIMAs, unless large load of
tyramine
 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 : 1st line

• relatively little affinity for dopamine,

histamine, alpha-adrenergic and cholinergic
receptors : hence better side effect profile
• relatively safe in overdose
 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
 SSRIs

• 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.

•
 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
 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
dysfunction
• useful in depression with insomnia
• but higher doses needed for antidepressant
effects
 NaSSA
(mirtazapine)
• noradenergic & specific serotonergic
• 5HT2 & 5HT3 antagonist (more sedating,
less GI SEs, weight gain)
• used in depression with anxiety, insomnia,
weight loss.
• 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
• lactation : TCAs (most evidence), SSRIs(no
major SE on infants)

•
 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
sertraline
• MAOi :If necessary, use 30-50% dose
 renal disease

• avoid venlafaxine and fluoxetine in severe

disease
 epilepsy

• TCAs lower seizure threshold

• SSRIs first choice
 adequate trial

• atleast 6 weeks of the highest tolerated

dose (upto BNF maximum)
• failure of adequate trial occurs in upto 25%
patients
 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
treatment
Maintenance : recurrent
episodes

• if period b/w episodes <3yrs or severe

episodes(marked suicidal thoughts), treat
for atleast 5 years (often indefinitely)