Depression Flashcards
TCAs. Examples and MOA
Tricyclic antidepressants E.g. Amitriptyline, dothiepin (dosulepin), lofepramine, nortriptyline Inhibit neuronal uptake of NA and 5-HT, leading to augmented concentrations in the synaptic cleft. The increase in catecholamines may lead to down-regulation of presynaptic alpha-2-adrenoceptors and 5-HT receptors and post synaptic beta-adrenoceptors. Exhibit binding at a range of receptors including muscarinic receptors, histamine, alpha-1-adrenoceptors and 5-HT receptors. Many TCAs are sedating and dangerous in overdose Antimuscarinic effects (these limit their tolerability) Dry mouth Blurred vision Constipation Urinary retention
TCAs. Side effects
Sedation (esp Amitriptyline) is a major problem but can be a reason to choose a TCA if sleep is impaired. May cause cardiac effects such as QT interval prolongation, and the potentiation of catecholamines also predisposes to heart block and arrhythmias. (Dangerous in overdose) Not suitable for patients with IHD, >70yrs, or at high risk of attempting suicide. Amitriptyline is useful in neuropathic pain, prophylaxis of migraine and IBS (at low doses).
NARIs. Example and MOA.
NA reuptake inhibitors. E.g. Reboxetine Selectively inhibit NA reuptake Useful in patients who cannot take TCAs but are resistant to effect of SSRIs.
SNRIs. Example and MOA.
Serotonin- NA reuptake inhibitors E.g. Venlafaxine Inhibits serotonin and NA reuptake but fails to bind to additional receptors - fewer side effects (lack of sedative and anti muscarinic side effects but does cause GI side effects). Associated with causing HTN.
NaSSAs. Example and MOA.
Noradrenergic and specific serotontinergic antidepresssants E.g. Mirtazapine Exhibits alpha-2-adrenoceptor antagonist activity, inhibiting negative feedback by these presynaptic receptors and this producing an increase in NA and 5-HT transmission. Sedation in early treatment but antimuscarinic side effects are limited.
SRMs. Examples and MOS.
Serotonin receptor modulators E.g. Nefazodone and trazodone Inhibition of serotontin reuptake and the selective inhibition of post synaptic serotonin receptors.
MAOs. Examples and MOA.
E.g. Isocarboxazid, moclobemide, phenelzine, tranylcypromine Rarely used now Inhibit monoamine oxidases, thus preventing the breakdown of monoamine NTs and increasing their concentration. MAOIs also prevent breakdown of indirectly acting sympathomimetic amine, tyramine (from diet) - it causes release of catecholamines and leads to a HTN. Tyramine is present in certain foods such as yeast extracts, wines and beers, avocado, banana, pickled herring and cheeses and this response is known as the CHEESE REACTION. Most act irreversibly - effect may persist for 2-3 weeks after the cessation of treatment. Moclobemide, a selective reversible inhibitor of MAO-A (RIMA) reduced interactions with food since tyramine is metabolised by MAO-B.
Clinical use of antidepressants
Mild depression - watchful waiting, patient reassessed after 2 weeks. Initial antidepressant treatment is not recommended. NICE: SSRI (e.g. Fluoxetine) as 1st line (if impaired sleep use sedating TCA) Initial treatment fails –> swap to another SSRI (or another drug class) Treatment should be continued at least 6 months after remission If patient had 2 recent depressed episodes, treatment should be continued for 2 years. TCAs toxic in overdose - avoid if high suicide risk. Antidepressants not associate with tolerance/ cravings but may be withdrawal symptoms (reduced dose over 4 weeks or longer esp. With paroxetine). SSRIs and TCAs equally effective Antidepressants take approx 2 weeks for effect to occur. Psych treatment must be considered e.g. CBT CBT might be only therapy for mild depression.
St John’s Wort
Possible effective antidepressant Similar mechanism at SSRIs NOT to be used with congenital antidepressant die to side effects and increased toxicity with SSRIs It is an enzyme inducer (many INTERACTIONS) Warfarin Carbamazepine/ phenytoin Anti HIV Ciclosporin Oral contraceptives These drugs may become less effective Depression should be managed under medical supervision
Depression treatment pathway
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Bipolar affective disorder treatment first line
“Manic depression” LITHIUM remind first line agent for acute and prophylaxis of bipolar. Unclear MOA. Lithium should be avoided in rents impairment Narrow therapeutic window - range of interactions and requires therapeutic drug monitoring.
Bipolar disorder. Anticonvulsants.
E.g. Carbamazepine and valproate Carbamazepine and valproate are used in second line as prophylactic mood stabilisers in bipolar disorder. Anticonvulsants, lamotrigine and gabapentin have an unlicensed role in bipolar affective disorder when other treatments have failed.
Bipolar disorder. Neuroleptics (antipsychotics)
E.g. Haloperidol and chloropromazine Neuroleptics may be used to control psychotic symptoms, which may be associated with depression and particularly during the manic phase of bipolar disorder.
Anxiety treatment general.
Drugs to offer symptomatic relief Use of antidepressants may improve long term outcome
Anxiety. Beta blockers.
Propranolol most commonly used to react physical symptoms (associated with beta adrenoceptors activation) Sx include sweating/ palpitations/ tremor/ tachycardia.
