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Anti-depressants Or What When Dr Bruce Davies www.bradfordvts.co.uk Range Tricyclics Tetracyclics SSRI SNRI MAOI Oddities Adjuvants Factors Influencing Choice Features of illness, e.g. agitation, hypersomia Suicide risk Other therapy Other illness. Side effects Cost Special problems e.g. Age, driving, pregnancy Drug Failure Non compliance. Inadequate dosage. Other drugs e.g. alcohol, caffeine. Unresolved outside problems. Up to 25% failure even if above don’t apply. Tricyclics Amitryptyline Potent sedative Weight gain ++ Anticholinergic ++ Most researched 150mg / day (Therapeutic in 95% of adults) Clomipramine Similar side effects to amitryptyline. Said to be best for obsessional symptoms. 150mg / day Tricyclics Dothiepin Sedative Same side effects as amitryptyline. By far and away the most toxic antidepressant. 150 mg / day Imipramine Stimulant Anticholinergic ++ 150 mg/ day Tricyclics Lofepramine Least toxic TCA. Minimal sedative side effects. Anticholinergic + Doubts about efficacy. 210 mg / day Protriptyline Stimulant. Anticholinergic + 40mg / day Tetracyclics Maprotiline Similar side effect profile to amitryptyline. Seizures severe in overdose. 150 mg /day Mianserin Good safety in overdose. Few sedative or anticholinergic properties. ? Agranulocytosis risk 90 mg / day SSRI First choice in elderly. First choice if heart disease. First choice if suicide risk. More expensive. ? Side effects Like TCA reduce with time. Gut problems predominate. Flat dose response curve – so no need to titrate dose upwards. SSRI Citalopram Few interactions Fluoxetine Sedation – Skin s/e Fluvoxamine Gut s/e + Most expensive Anxiety + Cheapest Insomnia - 20 mg /day Paroxetine Sedation + Sertraline Diarrhoea Withdrawal 20 mg /day problems ? 50 mg /day 20-80 mg /day 200 mg /day SSNRI Venlafaxine Selective Serotonin and noradrenaline reuptake inhibitor – like amitryptyline. Few other effects – unlike amitryptyline. 75-150mg / day minimum Dry mouth, somnolence, high BP, nausea, headache and dizziness. MAOI The old ones block peripheral MAOI ( B ) and central MAOI (A) so a low tyramine diet is needed. ? Obsolete. Moclobemide. Only MAOI-A. ? Role. ? Special place in anxiety disorder. 300-600mg / day. Oddities Trazodone. Unique structure. Low cardiotoxicity, few anticholinergic side effects. Drowsiness +. Nausea. 150 mg /day. Oddities Tryptophan Natural amino acid - Serotonin precursor. Eosinophilia-myalgia syndrome, Hospital initiation only. Adjuvant to others ? Flupenthixol Some doubts as to efficacy. Fast action 1 mg / day Adjuvants and Combinations Realm of specialists Lithium, carbamazepine Mixtures i.e. SSRI and TCA Dangerous – need expert supervision Anxiety Usually worth trying a antidepressant. May be useful to avoid the stimulant ones ! May need higher doses. Initiation may lead to paradoxical increase in symptoms. ? Cover with short course of anxiolytic. Anxiety ? Role of benzodiazepines. ? Beta-blockers. Buspirone. Some efficacy, but small. Slow onset, 2-4 weeks. DSM - IV Duration > 2 weeks Depressed mood or Marked loss of interest or pleasure in normal activities Plus 4 of: i. Significant change in weight ii. Significant change in sleep pattern iii. Agitation or retardation iv. Fatigue or loss of energy v. Guilt / worthlessness vi. Can’t concentrate or make decisions vii.Thoughts of death or suicide Incidence Of Depression: 2000 Patients 100 - major 100 - minor 200 subclinical Depression. In 50% of patients it may not be acknowledged. ICD - 10 Patient has low mood: 1) How bad is it and how long has it been going on? 2) Have you lost interest in things? 3) Are you more tired than usual? ICD - 10 Mild Two criteria from 1-3 and 2 others. Moderate Two criteria from 1-3 and 3-4 others or a yes to question 5. Severe Most of the criteria in severe form especially questions 5 & 9. BUT BUT BUT But there is a lot more than the drugs. The use of other therapies is equally important. The doctor may be the best drug. Availability is often the limit to other treatment methods. Based On BNF June 2000. Depression in General Practice. Tylee, Priest & Roberts. Pub. Martin Dunitz. 1996. GP Psychotropic Handbook. S Bazire. Quay Books. 1995. Basic Notes in Psychiatry. Michael Levi. Kluwer Books. 1997.