Old drugs in modern psychogeriatry

Transcription

1 Old drugs in modern psychogeriatry Some historical events in psychopharmacology Chemotherapy of depression Commonly used hypnotics and anti-anxiety ( minor tranquilizers ) Anti-psychotics ( major tranquilizers ) Mood stabilizers 1

2 2 Some Historical Events in Psychopharmacology Hashish intoxication proposed as a model of insanity (Moreau) Chloral hydrate introduced as a treatment for melancholia and mania Cocaine proposed as a treatment in psychiatry ( Freud ) Paraldehyde introduced Research with morphine, alcohol, ether, and paraldehyde in normal individuals ( Kraepelin ) 193- Barbiturates introduced Psychosis of syphilis treated with malaria fever therapy ( Julius von Warner Jauregg ) Barbiturate-induced coma ( Jacob Klaesi ) Insulin shock for schizophrenia (Manfred Sakel )

3 Some Historical Events in Psychopharmacology (2) Rauwolfia serpentina (reserpine ) introduced.treatment in schizophrenia Pentylenetrazol-induced convulsions ( Laszlo von Meduna ) Frontal lobotomies ( Egas Monitz ) Electroconvulsive therapy ( Ugo Cerletti and Luciano Bini ) Dilantin introduced as anticonvulsant (Tracy Putnam ) 1943 Lysergic acid diethylamide (LSD)synthesized( Albert Hoffman ) Lithium introduced Chlorpromazine introduced Tricyclic antidepressants and monoamine oxidase inhibitors introduced 196 Chlordiazepoxide introduced ( Nirvaxal ) 3

4 OLD DRUGS IN MODERN PSYCHOGERIATRY CHEMOTHERAPY OF DEPRESSION SEVERITY AND DURATION OF DEPRESSION DEPRESSION RESULTS FROM DISORDER OF NEUROTRANSMISION ANTIDEPRESSANTS PRESCRIBED IN ADEQUQTE DOSES CORRECT ABNORMAL NEUROTRANSMISION CHOICE OF ANTIDEPRESSANTS NEUROTRANSMITER ACTION ( MAJOR/MAINOR REUPTAKE INHIBITION ) S=serotonin, N= norepinephrine NORTRIPTYLINE HAS THERAPEUTIC WINDOW IN PSYCHOTIC DEPRESSION start high-potency neuroleptics first then add antidepressants THERAPY SHOULD CONTINUE FOR 6 TO 12 MONTH 4

5 TRICYCLIC, HETEROCICLYC AND SELECTIVE SEROTONIN ANTIDEPRESSANTS HIGH-SEDATING AMITRIPTILINE (S/N) (Elatrol ) DOXEPIN (S/N) ( Gilex ) MAPROTILINE (N) ( Melodil, Ludiomil ) TRAZODONE (S) ( Trazodil ) CLOMIPRAMINE (S/N) ( Anafranil,Maronil) LOW-SEDATING DESIPRAMINE( N) (Deprexan ) IMIPRAMINE (S/N) ( Primonil, Tofranil ) NORTRIPTYLINE ( Nortylin ) LOW SEDATING NOT-ANTICHOLINERGIC SSRI FLUOXETINE (Prozac ) FLUVOXAMINE (Favoxil) PAROXETINE (Seroxat) SERTRALINE (Lustral ) SNRI DULOXETINE (Cymbalta ) SSRINDA VENLAFAZINE (Efexor) 5

6 TYPES OF ANTIDEPRESSANTS 1. NOREPINEPHRINE (noradrenaline) SEROTONINE reuptake inhibitors : tryciclics,venlafaxine (high doses) 2. SEROTONIN reuptake inhibitors : SSRI, venlafaxine (low doses) 3. NOREPINEPHRINE (NORADRENALINE) reuptake inhibitors : reboxetine 4. 5-HT2 receptor blockade plus serotonin reuptake inhibition : nefadozone, trazodone 5. MONOAMINE OXIDASE INHIBITON : moclobemide 6. Pre-synaptic alpha-2- autoreceptor and heteroreceptor blockade : mitrazepine 7. SEROTONIN PRECURSOR: tryptophan 6

7 7 Antidepressants relative side effects(1) OTHER proconv ulsant overdose sedation nausea cardiac anticholin ergic 2-6 TRAZODONE 15-6 MITRAZAPINE 15-9 MIANSERINE 5-2 SERTRALINE 2-5 PAROXETINE 15-3 FLUVOXAMINE 2-6 FLUOXETINE 2-6 CITALOPRAM SSRI 4-2 NORTRIPTYLINE MAPROTILINE 15-3 IMIPRAMINE 15-3 DOXEPIN CLOMIPRAMINE 15-3 AMITRIPTILINE TRICYCLICS Relative side effects at average dose Adult max dose mg/day drug

8 Antidepressants relative side-effects(2) Drug PHENELZINE MOCLOBEMIDE Adult max dose mg/day 9 6 anticholin ergic cardiac Relative side effects at average dose nausea sedation MONO-AMINE-OXIDASE INHIBITORS overdose procon vulsant? NSRI VENLAFAXINE ? NARI REBOXETINE 4-8 8

9 General minimum treatment :duration recommendations FIRST EPISODE : 6 12 month post-recovery SECOND EPISODE: 2-3 years THIRD EPISODE : 5 years or longer Withdrawal of therapy Slowly reduce doses of a minimum of four weeks 9

10 SIDE EFFECTS OF ANTIDEPRESSANTS DRUGS CYCLIC ANTIDEPRESSANTS DROWSINESS DRY MOUTH CONSTIPATION TREMOR SPEECH BLOKAGE SEXUAL DISFUNCTION INCREASED SWEATING POSTURAL HYPOTENSION TACHICARDIA CARDIAC ARRHYTMIAS SSRI NERVOUSNESS INSOMNIA NAUSEA DIARRHEA HEADACHE SEXUAL DISFUNCTION 1

11 HIGH- ANTICHOLINERGIC AMITRIPTILINE(S/N) IMIPRAMINE (S/N) CLOMIPRAMINE (S/N) LOW- ANTICHOLINERGIC DESIPRAMINE (N) MAPROTILINE(N) TRAZODONE(S) 11

12 Commonly used sedative-hypnotic-minor tranquilizers Usual oral sedative dose Barbiturates Usual oral hypnotic dose Usual maximum daily oral dose PHENOBARBITAL 15-3 mg 15mg 3-4mg Non barbiturate sedative hypnotics CHLORAL HIDRATE 25mg 5-1mg PARALDEHYDE 5-1cc 2-3cc Benzodiazepines DIAZEPAM (Valium ) 2-1mg 2-3mg CHLORDIAZEPOXIDE(Librium) 5-25mg 5-1mg OXAZEPAM ( Vaben ) 1-3mg 3-6mg 2. gm 1cc 5mg 75-1mg 9mg CHLORAZEPATE(Tranxal ) 7,5mg-15mg 3mg 4mg Miscellaneous MEPROBAMATE 2-4mg 8mg 1,2gm DOXEPIN (Gilex) 12 25mg 5-1mg 3mg

13 CHLORPROMAZINE THIORIDAZINE PERPHENAZINE TRIFLUOPHENAZINE FLUPHENAZINE CHLORPROTHIXENE HALOPERIDOL Commonly used major tranquilizers Chlorpromazine ratio 1:1 1:1 1:1 1:2 1:5 1:1 1:5 Usual Daily Oral dose PHENOTHIAZINES 1-2mg 1-2mg 8-16mg 5-1mg 2mg THIOXANTHENES 1-2mg BUTIROPHENONE 2-5mg Usual Daily maximum Dose 1gm 6mg 32mg 2mg 1mg 6mg 15mg 13

14 ANXIOLITICS DRUGS APRAZOLAN BROMAZEPAM LORAZEPAM OXAZEPAM CHLORDIAZEPOXIDE CHLORAZEPATE DIAZEPAM Average dose mg/day Adult maximum dose mg/day Shorter acting benzodiazepines Longer acting benzodiazepines Drowsiness Dependence potential Beta-blockers PROPRANOLOL 8 16 O Other anxiolytics BUSPIRONE O O

15 ANTIPSYCHOTICS-relative side effects Relative side-effects at average dose DRUG Dose mg/day anticholinergic cardiac EPSE hypotension sedation phenotiazines CHLORPROMAZINE 1g LEVOMEPROMAZINE 1g PROMAZINE 8 THIORIDAZINE 8 FLUPHENAZINE 2 PERPHENAZINE 24 butirophenones HALOPERIDOL 2 others SULPIRIDE 24 15

16 ANTIPSYCHOTICS-relative side effects (2) Relative side-effects at average dose DRUG Dose mg/day anticholinergic cardiac EPSE hypotension sedation Atypical CLOZAPINE 9 OLANZEPINE 2 RISPERIDONE 8 Depo Injection FLUPENAZINE 1-2 weeks HALOPERIDOL 3-4 weeks RISPERDONE 16

17 Characteristics of BDZ users OLDER MEDICALLY ILL PSYCHIATRIC PATIENTS WITH PANIC OR AGORAPHOBIC DISORDERS PSYCHIATRIC PATIENTS WITH RECURRENT DYSPHORIA CHRONIC SLEEP DISORDERED PATIENTS 17

18 Patients where withdrawal should not be attempted Elderly maintained symptom free by low and unchanging doses. Chronic physical disorders controlled by BDZ. Where quality of life is improved. 18

19 Withdrawal symptoms in the dependent patient Mild Psychological : tension, restlessness, agitation Physical : dry mouth, sweating,tremor,head ache, nausea Mental : impaired memory and concentration Moderate Perceptual changes : hypersensitivity to light / sound Dysphoria, flu-like symptoms, anorexia, depression Severe (rare) Convulsions Psychosis Delusions 19

20 LITHIUM MOOD STABILAIZERS Side effects : weight gain, cognitive dulling Plasma levels,5-1,2mmol/l ( in elderly 1/3-1/2 less) The main reason for lithium failure sis non-compliance. CARABAMAZEPINE Levels of 7mg/l or above are strongly associated with therapeutic response in bipolar patients. SODIUM VALPORATE Levels of 5-1mg/l are strongly associated with therapeutic response in bipolar patients. LAMOTRIGENE 2