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PHARMACOTHERAPY OF MOOD DISORDERS
DR GIAN LIPPI CONSULTANT PSYCHIATRIST UNIVERSITY OF PRETORIA & WESKOPPIES HOSPITAL FORENSIC UNIT
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CONTENTS BASIC BACKGROUND PHYSIOLOGY
BASICS OF PHARMACOTHERAPY OF MOOD DISORDERS ANTIDEPRESSANTS (ALL THE CLASSES) MOOD STABILIZERS (ALL THE CLASSES)
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BASIC BACKGROUND PHYSIOLOGY
PRESYNAPTIC SYNAPSE POSTSYNAPTIC MAO / COMT NEURON EFFECT RECEPTOR NEUROTRANSMITTER
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BASICS ANTIDEPRESSANTS ARE THE MAINSTAY OF TREATMENT OF MAJOR DEPRESSIVE DISORDER (MDD) - SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIs) - SEROTONIN NORADRENALIN REUPTAKE INHIBITORS (SNRIs) - SELECTIVE NORADRENALIN REUPTAKE INHIBITORS (NRIs) - NORADRENALIN DOPAMINE REUPTAKE INHIBITORS (NDRIs) - TRICYCLIC ANTIDEPRESSANTS (TADs) - TETRACYCLIC ANTIDEPRESSANTS (TTADs) - MONOAMINE OXIDASE INHIBITORS (MAOIs) - REVERSIBLE INHIBITORS OF MONOAMINE OXIDASE (RIMAs) - NORADRENALIN & SPECIFIC SEROTONIN ANTAGONISTS (NASSAs) - SEROTONIN ANTAGONIST / REUPTAKE INHIBITORS (SARIs) -MELATONIN ANTAGONISTS (MAs) MOOD STABILIZERS ARE THE MAINSTAY OF TREATMENT OF THE BIPOLAR DISORDERS - CLASSIC MOOD STABILIZER - ANTICONVULSANTS - ATYPICAL ANTIPSYCHOTICS
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ANTIDEPRESSANTS
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SSRIs, MECHANISM OF ACTION
PRESYNAPTIC SYNAPSE POSTSYNAPTIC MAO / COMT NEURON EFFECT RECEPTOR NEUROTRANSMITTER
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SSRIs, GENERAL 1ST LINE TREATMENT FOR MDD DRUGS & DOSAGES
- FLUOXETINE mg po mane - PAROXETINE mg po mane (AKA Prozac) - CITALOPRAM mg po mane - ESCITALOPRAM mg po mane - SERTRALINE mg po mane - FLUVOXAMINE mg po bd MOST COMMON SIDE-EFFECTS - SEXUAL DYSFUNCTION (DECREASED LIBIDO, ANORGASMIA, erectile dysfunction) - NAUSEA, VOMITING, DIARRHOEA - HEADACHE - INSOMNIA
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SNRIs, MECHANISM OF ACTION
PRESYNAPTIC SYNAPSE POSTSYNAPTIC MAO / COMT NEURON EFFECT RECEPTOR NEUROTRANSMITTER
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SNRIs, GENERAL MOSTLY 2ND LINE TREATMENT FOR MDD
FOR TREATMENT AUGMENTATION, TREATMENT RESISTANT MDD & MDD WITH PROMINENT PAIN SYMPTOMS DRUGS & DOSAGES - VENLAFAXINE mg po mane - DULOXETINE mg po mane MOST COMMON SIDE-EFFECTS - GASTROINTESTINAL DISCOMFORT - SEXUAL DYSFUNCTION - SEDATION - HYPOTENSION & TACHYCARDIA - DRY MOUTH
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NRIs, MECHANISM OF ACTION
PRESYNAPTIC SYNAPSE POSTSYNAPTIC MAO / COMT NEURON EFFECT RECEPTOR NEUROTRANSMITTER
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NRIs, GENERAL MOSTLY INEFFECTIVE AS AN ANTIDEPRESSANT
FOR AUGMENTATION TREATMENT IN MDD DRUGS & DOSAGES - REBOXETINE 4 - 5mg po bd MOST COMMON SIDE-EFFECTS - URINARY HESITANCY - CONSTIPATION - HEADACHE - NASAL CONGESTION - PERSPIRATION - DRY MOUTH - DIZZINESS - DECREASED LIBIDO - INSOMNIA
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NDRIs, MECHANISM OF ACTION
PRESYNAPTIC SYNAPSE POSTSYNAPTIC MAO / COMT NEURON EFFECT RECEPTOR NEUROTRANSMITTER
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NDRIs, GENERAL MOSTLY 2ND LINE ANTIDEPRESSANT
FOR TREATMENT AUGMENTATION, MDD WITH PROMINENT HYPERSOMNIA & FATIGUE OR PATIENTS WITH SEXUAL DYSFUNCTION ON OTHER ANTIDEPRESSANTS DRUGS & DOSAGES - BUPROPION mg po mane ( can also be used for smoking cessation) MOST COMMON SIDE-EFFECTS - HEADACHE - INSOMNIA - NAUSEA
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TADs & TTADs, MECHANISM OF ACTION
PRESYNAPTIC SYNAPSE POSTSYNAPTIC MAO / COMT NEURON EFFECT RECEPTOR NEUROTRANSMITTER
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TADs & TTADs, GENERAL MOSTLY 2ND LINE ANTIDEPRESSANTS DUE TO LESS TOLERABLE SIDE-EFFECTS & RISK OF LETHAL ARRHYTHMIA WITH OVERDOSE EFFECTIVE ANTIDEPRESSANTS TADs - AMITRIPTYLINE mg po nocte - CLOMIPRAMINE mg po nocte - IMIPRAMINE mg po nocte - TRIMIPRAMINE mg po nocte - LOFEPRAMINE mg po nocte (mostly used currently) TTADs - MAPROTILINE mg po nocte (hardly used currently) MOST COMMON SIDE-EFFECTS - ANTICHOLINERGIC SIDE – EFFECTS, OFTEN SEVERE (CONSTIPATION, URINARY RETENTION, DRY MOUTH, BLURRED VISION) - SEDATION - ORTHOSTATIC HYPOTENSION - CARDIAC ARRHYTHMIAS WHICH CAN BE LETHAL IN OVERDOSES (MORE WITH TADs)
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MAOIs & RIMAs, MECHANISM OF ACTION
PRESYNAPTIC SYNAPSE POSTSYNAPTIC MAO / COMT NEURON EFFECT RECEPTOR NEUROTRANSMITTER
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MAOIs & RIMAs, GENERAL POWERFUL ANTIDEPRESSANTS NOT FOR 1ST LINE TREATMENT MAOIs - TRANYLCIPROMINE mg po bd RIMAs - MOCLOBEMIDE mg po bd MOST COMMON SIDE-EFFECTS - ORTHOSTATIC HYPOTENSION - INSOMNIA - WEIGHT GAIN - OEDEMA - SEXUAL DYSFUNCTION TYRAMINE-INDUCED HYPERTENSIVE CRISIS - CAUSED BY INTAKE OF TYRAMINE – CONTAINING FOODS WHILST ON THE MEDICATION - SUCH FOODS MUST BE AVOIDED, THESE INCLUDE AGED CHEESES, FISH, BILTONG, MARMITE, SAUERKRAUT, BEER, CHIATI WINE, LIQUEUR
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NASSAs, MECHANISM OF ACTION
PRESYNAPTIC SYNAPSE POSTSYNAPTIC MAO / COMT NEURON EFFECT RECEPTOR NEUROTRANSMITTER
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NASSAs, GENERAL CAN BE USED AS 1ST / 2ND LINE TREATMENT, OR IN AUGMENTATION TREATMENT OF MDD OFTEN USED IN TREATMENT OF MDD WITH PROMINENT INSOMNIA DRUGS & DOSAGES - MIRTAZAPINE mg po nocte MOST COMMON SIDE-EFFECTS - SEDATION - WEIGHT GAIN - INCREASED APPETITE - DRY MOUTH
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SARIs, MECHANISM OF ACTION
PRESYNAPTIC SYNAPSE POSTSYNAPTIC MAO / COMT NEURON EFFECT RECEPTOR NEUROTRANSMITTER
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SARIs, GENERAL NOT 1ST LINE TREATMENT IN MDD
MOSTLY INEFFECTIVE IN THE TREATMENT OF MDD OFTEN USED IN TREATMENT OF MDD WITH PROMINENT INSOMNIA DRUGS & DOSAGES - TRAZODONE mg po bd MOST COMMON SIDE-EFFECTS - SEDATION - ORTHOSTATIC HYPOTENSION - DIZZINESS - HEADACHE - NAUSEA
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MAs, MECHANISM OF ACTION
PRESYNAPTIC SYNAPSE POSTSYNAPTIC MAO / COMT NEURON EFFECT RECEPTOR NEUROTRANSMITTER 22
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MAs, GENERAL - AGOMELATINE 25-50mg po nocte - DIZZINESS - NAUSEA 23
NOT 1ST LINE TREATMENT IN MDD OFTEN USED IN TREATMENT OF MDD WITH PROMINENT INSOMNIA DRUGS & DOSAGES - AGOMELATINE 25-50mg po nocte MOST COMMON SIDE-EFFECTS - DIZZINESS - NAUSEA 23
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MOOD STABILIZERS
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INDICATIONS & CATEGORIZATION
TREATMENT OF THE MAINTENANCE PHASE OF BIPOLAR DISORDERS TREATMENT OF MANIC EPISODES TREATMENT OF HYPOMANIC EPISODES TREATMENT OF DEPRESSIVE EPISODES TREATMENT OF MIXED EPISODES 3 GROUPS OF MOOD STABILIZERS - CLASSIC MOOD STABILIZER - ANTICONVULSANTS - ATYPICAL ANTIPSYCHOTICS
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CLASSIC MOOD STABILIZER
LITHIUM INDICATIONS - 1ST LINE TREATMENT OPTION IN BIPOLAR DISORDERS (MAINTENACE PHASE) - MOST EFFECTIVE IN TREATING & PREVENTING MANIC EPISODES - CAN BE CONSIDERED FOR TREATMENT OF MIXED EPISODES & RAPID CYCLING, BUT NOT 1ST LINE - QUESTIONABLE EFFICACY IN TREATMENT, NOT PREVENTION OF BIPOLAR DEPRESSION DOSAGE, THERAPEUTIC INDEX & MONITORING OF LITHIUM BLOOD LEVELS - DOSE IS ACCORDING TO TROUGH LEVEL OF LITHIUM IN THE BLOOD - START AT LOW DOSE, INCREASE SLOWLY & ADJUST DOSE ACCORDING TO LITHIUM LEVEL - SAFE STARTING DOSE IS 500mg po mane - LITHIUM HAS A VERY NARROW THERAPEUTIC INDEX: LITHIUM LEVEL OF 0,5 – 0.9 FOR THE MAINTENANCE PHASE LITHIUM LEVEL OF UP TO 1,5 FOR THE TREATMENT OF A MANIC EPISODE (ACUTE) - LEVELS BELOW THIS RANGE RESULTS IN TOTALLY INEFFECTIVE TREATMENT - LEVELS ABOVE THIS RANGE CAN RESULT IN POTENTIALLY LETHAL LITHIUM TOXICITY - LITHIUM LEVELS NEED TO BE CHECKED 4 DAYS AFTER STARTING TREATMENT OR CHANGING DOSE - LITHIUM LEVELS NEED TO BE CHECKED 6-MONTHLY WHEN A PATIENT IN THE MAINTENANCE PHASE HAS STABLE BLOOD LEVELS WITHIN THE THERAPEUTIC RANGE - LITHIUM BLOOD LEVELS ARE TROUGH LEVELS, SO WHEN BLOOD IS DRAWN TO TO CHECK THE LEVELS, IT MUST BE DRAWN JUST BEFORE THE NEXT DOSE
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CLASSIC MOOD STABILIZER
LITHIUM MOST COMMON SIDE-EFFECTS - NAUSEA, VOMITING, DIARRHOEA - WEIGHT GAIN & FLUID RETENTION - POSTURAL TREMOR - RENAL EFFECTS: POLYURIA WITH SECONDARY POLYDIPSIA HYPOKALAEMIA RARELY NONSPECIFIC INTERSTITIAL FIBROSIS WITH MORE THAN 10 YEARS OF LITHIUM USE - BENIGN, USUALLY REVERSIBLE THYROID EFFECTS: MOST COMMONLY HYPOTHYROIDISM HYPERTHYROIDISM GOITER & EXOPHTHALMUS - CARDIAC EFFECTS SECONDARY TO HYPOKALAEMIA: T-WAVE FLATTENING OR INVERSION ON ECG SINUS DYSRHYTHMIAS, HEART BLOCK, SYNCOPE EPISODES - TERATOGENESIS: CAN CAUSE EBSTEIN’S ANOMALY IN THE UNBORN FETUS OF A PREGNANT MOTHER ON LITHIUM LITHIUM TOXICITY - TREMOR, DYSARTHRIA, ATAXIA - NAUSEA, VOMITING, DIARRHOEA - CARDIOVASCULAR CHANGES & RENAL DYSFUNCTION - MYOCLONUS & MUSCULAR FASCICULATIONS - SEIZURES, IMPAIRED LEVEL OF CONSCIOUSNESS, COMA - MEDICAL EMERGENCY, TREAT BY STOPPING LITHIUM & PUSHING INTRAVENOUS FLUIDS
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CLASSIC MOOD STABILIZER
LITHIUM BEFORE STARTING A PATIENT ON LITHIUM THE FOLLOWING SPECIAL INVESTIGATIONS NEED TO BE DONE TO CHECK IF HE/SHE IS A SUITABLE CANDIDATE FOR THE TREATMENT: - UKE (CHECK POTASSIUM & SIFT FOR KIDNEY DYSFUNCTION) - CREATININE CLEARANCE (LITHIUM IS EXCRETED EXCLUSIVELY BY THE KIDNEYS, KIDNEY FUNCTION NEEDS TO BE INTACT) - FBC (CHECK LEUCOCYTES TO GET A BASELINE VALUE, LITHIUM CAN CAUSE LEUCOCYTOSIS) - TSH (CHECK FOR HYPO/HYPERTHYROIDISM, LITHIUM CAN INTERFERE WITH THYROID FUNCTION) - ß-HCG IN FEMALES (LITHIUM IS TERATOGENIC) - ECG (CHECK FOR DYSRHYTHMIA /HEART BLOCK) MONITORING OF THE PATIENT ON LITHIUM - UKE (IN 1ST MONTH AFTER STARTING LITHIUM, THEN 6-MONTHLY IF NORMAL TO MONITOR POTASSIUM & LONG-TERM KIDNEY FUNCTION WHICH CAN DETERIORATE ON CHRONIC LITHIUM TREATMENT) - FBC (PERIODICALLY TO CHECK FOR LEUCOCYTOSIS) - TSH (IN 1ST MONTH AFTER STARTING LITHIUM, THEN 6-MONTHLY IF NORMAL TO CHECK FOR HYPO/HYPERTHYROIDISM) - ß-HCG IN FEMALES (PERIODICALLY TO CHECK FOR PREGNANCY) - ECG (IN 1ST MONTH AFTER STARTING LITHIUM, THEN PERIODICALLY TO CHECK FOR T-WAVE FLATTENING OR INVERSION, DYSRHYTHMIA/HEART BLOCK) - LITHIUM LEVELS (4 DAYS AFTER STARTING LITHIUM/CHANGING DOSE, THEN 3-6 MONTHLY TO CHECK FOR TOXICITY/SUB-THRESHOLD DOSING/NEED FOR DOSAGE ADJUSTMENT)
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ANTICONVULSANTS VALPROATE
INDICATIONS - 1ST LINE TREATMENT OPTION IN BIPOLAR DISORDERS (MAINTENANCE PHASE) - MOST EFFECTIVE IN TREATING & PREVENTING MANIC EPISODES - TREATMENT OF CHOICE FOR MIXED EPISODES & RAPID CYCLING - NOT EFFECTIVE IN TREATMENT & PREVENTION OF DEPRESSION - ADVANTAGE OF BEING ABLE TO TITRATE DOSE UPWARDS RAPIDLY DOSAGE mg po bd MOST COMMON SIDE-EFFECTS - SEDATION - WEIGHT GAIN - THROMBOCYTOPAENIA - HAIR LOSS AT HIGH DOSES - TREMOR MONITORING OF THE PATIENT ON VALPROATE - LFT (BEFORE STARTING TREATMENT TO CHECK FOR IMPAIRED LIVER FUNCTION SINCE VALPROATE IS METABOLIZED BY THE LIVER, THEN 6-MONTHLY TO CHECK FOR THE RARE SIDE-EFFECT OF POTENTIALLY FATAL HEPATOTOXICITY SEEN MOSTLY IN PAEDIATRIC PATIENTS)
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ANTICONVULSANTS CARBAMAZEPINE
INDICATIONS - FALLEN OUT OF FAVOUR, NO LONGER ROUTINELY USED, ONLY IN SPECIFIC CASES - SAME USE PROFILE AS VALPROATE BUT SEEMS TO BE LESS EFFECTIVE DOSAGE - STARTING DOSE 200mg po bd, TITRATE UP SLOWLY BY 200mg AT A TIME - MAINTENANCE DOSE mg po bd MOST COMMON SIDE-EFFECTS - RASH (EXFOLIATIVE DERMATITIS) - HYPONATREMIA & SYNDROME OF INAPPROPRIATE ADH SECRETION (SIADH) - GASTROINTESTINAL SIDE-EFFECTS - HEPATITIS - RARELY AGRANULOCYTOSIS/APLASTIC ANAEMIA (BONE MARROW SUPPRESSION) - INTERFERES WITH THE METABOLISM OF OTHER DRUGS MONITORING OF THE PATIENT ON CARBAMAZEPINE - LFT (BEFORE STARTING TREATMENT TO CHECK FOR IMPAIRED LIVER FUNCTION SINCE CARBAMAZEPINE IS METABOLIZED BY THE LIVER, THEN PERIODICALLY TO CHECK FOR HEPATITIS) - UKE (BASELINE BEFORE STARTING TREATMENT THEN PERIODICALLY TO CHECK FOR HYPONATREMIA & SIADH) - FBC (BASELINE BEFORE STARTING TREATMENT THEN PERIODICALLY TO CHECK TO CHECK FOR BONE MARROW SUPPRESSION)
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ANTICONVULSANTS LAMOTRIGINE
INDICATIONS - 1ST LINE TREATMENT OPTION FOR PATIENTS WITH PROMINENT BIPOLAR DEPRESSION - EFFECTIVE IN TREATING DEPRESSIVE EPISODES - TREATMENT OF CHOICE FOR PREVENTING DEPRESSIVE EPISODES - EFFECTIVE IN PREVENTING MANIC EPISODES - NOT EFFECTIVE IN TREATMENT OF MANIC EPISODES - POSSIBLE / QUESTIONABLE EFFICACY IN TREATMENT OF MIXED EPISODES & RAPID CYCLING DOSAGE - STARTING DOSE 25mg po nocte, TITRATE UP SLOWLY BY 25mg EVERY 2 WEEKS TO DECREASE THE RISK OF STEVENS-JOHNSON SYNDROME - MAINTENANCE DOSE mg po nocte MOST COMMON SIDE-EFFECTS - DIZZINESS & ATAXIA - BLURRED VISION & DIPLOPIA - HEADACHE - SEDATION - NAUSEA & VOMITING - STEVENS-JOHNSON SYNDROME (IF A RASH DEVELOPS, STOP LAMOTRIGINE IMMEDIATELY)
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ATYPICAL ANTIPSYCHOTICS
INDICATIONS - EFFECTIVE IN TREATMENT OF MANIC EPISODES - EFFECTIVE IN PREVENTING MANIC EPISODES - EFFECTIVE IN TREATING DEPRESSIVE EPISODES - NOT EFFECTIVE IN PREVENTING DEPRESSIVE EPISODES - CAN BE CONSIDERED FOR TREATMENT OF MIXED EPISODES & RAPID CYCLING, BUT NOT 1ST LINE DRUGS & DOSAGE - OLANZAPINE 10-20mg po nocte - QUETIAPINE mg po nocte - ARIPIPRAZOLE 10-30mg po nocte MOST COMMON SIDE-EFFECTS - METABOLIC SYNDROME (MS) – WEIGHT GAIN WITH CENTRAL OBESITY + HYPERTENSION + HYPERCHOLESTEROLAEMIA + HYPERGLYCAEMIA - OLANZAPINE – SEVERE MS, SEDATION, DIZZINESS, DRY MOUTH, CONSTIPATION, DYSPEPSIA, AKATHISIA - QUETIAPINE – MS, SEVERE SEDATION, DIZZINESS, POSTURAL HYPOTENSION - ARIPIPRAZOLE – HEADACHE, SEDATION, AKATHISIA, AGITATION, ANXIETY, DYSPEPSIA, NAUSEA NOT MS MONITORING OF THE PATIENT ON ATYPICAL ANTIPSYCHOTICS - BASELINE FASTING GLUCOSE & LIPOGRAM, BLOOD PRESSURE, WAIST CIRCUMFERENCE, WEIGHT MEASUREMENT - FASTING GLUCOSE & LIPOGRAM, BLOOD PRESSURE, WAIST CIRCUMFERENCE, WEIGHT MEASUREMENT 1 MONTH AFTER STARTING TREAMENT, THEN 6-MONTHLY - MORE REGULAR MONITORING FOR OLANZAPINE OR IF THERE ARE SIGNS OF MS
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THE END
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