Download Psychopharmacology of Mood Disorders

Psychopharmacology of Mood
Disorders
Dr. Bill Lyndon
Department of Psychological
Medicine, University of Sydney
Overview
• Antidepressants
• Antimanics
• Mood stabilisers
Antidepressants
• All antidepressants work by increasing the
availability of neurotransmitters serotonin
(5HT), noradrenaline (NA) or dopamine
(DA) in the synapse (acute effect), leading
to alterations in function of pre and postsynaptic receptors (chronic effect)
Antidepressants
• All antidepressants require 1 - 4 weeks of
chronic administration to produce
antidepressant effect
• All antidepressants have equal efficacy,
though some may be more effective for
certain patients and certain subtypes of
depression
Pharmacology of Antidepressants
• Tricyclics (amitriptyline, dothiepin etc)
• Irreversible MAOI’s (phenelzine)
• Reversible MAOI’s (moclobemide)
•
•
•
•
•
SSRI’s (fluoxetine, sertraline, citalopram etc)
SNRI’s (venlafaxine)
DA reuptake inhibitors (bupropion)
Selective NA reuptake inhibitors (reboxetine)
NaSSA’s (mirtazapine)
Sites of
Antidepressant
Action
B
5HT1A
A
(-)
(-)
5HT
M
A
O
(-)
A - MAOI’s
NE
B - SSRI’s
D
C - NARI’s
α2
(-)
D - mianserin
C
C+D - TCA”S, SNRI’s
Antidepressants
• Tricyclics:
(NA +/- 5HT reuptake inhibitors)
• developed 1950’s
– amitryptiline, imipramine, dothiepin
– effective but troublesome
– side effects (dry mouth, blurred vision,
sedation, postural hypotension)
– adverse effects (cardiotoxicity, seizures, lethal
in overdose)
Antidepressants
• Monoamine oxidase inhibitors (irreversible)
– introduced 1950’s
– effective but troublesome
– food interactions (tyramine) causing
hypertension
– multiple drug interactions (serotonin syndrome)
– side effects (postural hypotension, agitation,
insomnia, oedema)
Antidepressants
• Specific serotonin reuptake inhibitors
(SSRI’s):
– introduced 1990
– fluoxetine (Prozac), sertraline, paroxetine,
fluvoxamine, citalopram, escitalopram
– improved safety and side effect profile
– not free of side effects (agitation, nausea,
headache, insomnia, sexual dysfunction)
Antidepressants
• Serotonin and noradrenaline reuptake
inhibitors:
– venlafaxine
– similar safety and side effect profile to SSRI’s
– so-called dual action purported to be more
effective
– limited evidence from meta-analyses of
superior efficacy vs. SSRI’s
Antidepressants
• Reversible monoamine oxidase inhibitors:
– reversible
– No food or drug interactions at recommended
doses
– low incidence of side effects (nausea, agitation)
Antidepressants
• Others:
– NARI’s (reboxetine) - specific nradrenaline
reuptake inhibitor
– NaSSA (mirtazapine) - complex action leading
to increased synaptic NA and 5HT
– presynaptic α 2 blocker (mianserin) - blocks
inhibition of release of NA into synapse
Guidelines For Selection
•
•
•
•
•
•
•
•
Efficacy
Safety, Side Effect Profile
Medical comorbidity, drug interactions
Past History of Response
Long - Term Effects
Cost
Special Situations (pregnancy, young and old)
Compliance
Antimanics
• Lithium
• Antipsychotics
– Typical (haloperidol, chlorpromazine)
– Atypical (olanzapine, risperidone)
• Anticonvulsants
– sodium valproate (Epilim)
– carbamazepine (Tegretol)
Mood Stabilisers
• Used in bipolar disorder for prophylaxis of
both mania and depression
–
–
–
–
–
lithium
carbamazepine (Tegretol)
sodium valproate (Epilim)
lamotrigine (Lamictal)
other anticonvulsants
Lithium
• Discovered 1940’s (John Cade)
• Still mood stabiliser of first choice
• Proven efficacy in prophylaxis of mania and
depression (mania>depression)
Lithium
• Narrow therapeutic index - Li toxicity
• Side effect burden (nausea, tremor, weight
gain, acne, polyuria + polydipsia
• Adverse effects (hypothyroid, renal
damage)
• Problems in pregnancy, breast feeding
• Low patient acceptance (stigma, SE’s)
Anticonvulsants
• Less evidence base than for lithium
• Useful alternatives to Li especially in rapid
cycling disorder
• Generally better tolerated and safer
• Valproate, carbamazepine more effective
for preventing mania than depression
• Lamotrigine effective preventing depression
Mood Stabilisers
• Trend for combined therapy
– Li + anticonvulsant
– combined anticonvulsants
• Long term treatment required
– high relapse rate with discontinuation