Anti-depressants Or What When Dr Bruce Davies
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.
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 Tricyclics
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 Tetracyclics
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 ?
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: • Significant change in weight • Significant change in sleep pattern • Agitation or retardation • Fatigue or loss of energy • Guilt / worthlessness • Can’t concentrate or make decisions • 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: • How bad is it and how long has it been going on? • Have you lost interest in things? • Are you more tired than usual? • If the answer is yes to these, then: • Have you lost confidence in yourself? • Do you feel guilty about things? • Concentration difficulties? • Sleeping problems? • Change in appetite or weight? • Do you feel that life is not worth living any more?
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 BUTBUT • 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.