PHARMACOTHERAPY OF MOOD DISORDERS

DR GIAN LIPPI

CONSULTANT PSYCHIATRISTUNIVERSITY OF PRETORIA & WESKOPPIES HOSPITALFORENSIC UNIT

CONTENTS

BASIC BACKGROUND PHYSIOLOGY

BASICS OF PHARMACOTHERAPY OF MOOD DISORDERS

ANTIDEPRESSANTS (ALL THE CLASSES)

MOOD STABILIZERS (ALL THE CLASSES)

BASIC BACKGROUND PHYSIOLOGY

PRESYNAPTIC

MAO / COMT

POSTSYNAPTICSYNAPSE

EFFECT

RECEPTOR

NEUROTRANSMITTER

NEURON

BASICS

ANTIDEPRESSANTS ARE THE MAINSTAY OF TREATMENT OF MAJOR DEPRESSIVE DISORDER (MDD)

- SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIs)

MOOD STABILIZERS ARE THE MAINSTAY OF TREATMENT OF THE BIPOLAR DISORDERS

- SEROTONIN NORADRENALIN REUPTAKE INHIBITORS (SNRIs) - SELECTIVE NORADRENALIN REUPTAKE INHIBITORS (NRIs) - NORADRENALIN DOPAMINE REUPTAKE INHIBITORS (NDRIs) - TRICYCLIC ANTIDEPRESSANTS (TADs) - TETRACYCLIC ANTIDEPRESSANTS (TTADs)

- NORADRENALIN & SPECIFIC SEROTONIN ANTAGONISTS (NASSAs) - SEROTONIN ANTAGONIST / REUPTAKE INHIBITORS (SARIs)

-MELATONIN ANTAGONISTS (MAs)

- MONOAMINE OXIDASE INHIBITORS (MAOIs) - REVERSIBLE INHIBITORS OF MONOAMINE OXIDASE (RIMAs)

- CLASSIC MOOD STABILIZER - ANTICONVULSANTS - ATYPICAL ANTIPSYCHOTICS

ANTIDEPRESSANTS

SSRIs, MECHANISM OF ACTION

PRESYNAPTIC

MAO / COMT

POSTSYNAPTICSYNAPSE

EFFECT

RECEPTOR

NEUROTRANSMITTER

NEURON

SSRIs, GENERAL

DRUGS & DOSAGES - FLUOXETINE 20- 60mg po mane - PAROXETINE 20 - 50mg po mane (AKA Prozac) - CITALOPRAM 20 - 40mg po mane - ESCITALOPRAM 10 - 20mg po mane - SERTRALINE 50 - 200mg po mane - FLUVOXAMINE 50 - 150mg po bd

1ST LINE TREATMENT FOR MDD

MOST COMMON SIDE-EFFECTS - SEXUAL DYSFUNCTION (DECREASED LIBIDO, ANORGASMIA, erectile dysfunction) - NAUSEA, VOMITING, DIARRHOEA - HEADACHE - INSOMNIA

SNRIs, MECHANISM OF ACTION

PRESYNAPTIC

MAO / COMT

POSTSYNAPTICSYNAPSE

EFFECT

RECEPTOR

NEUROTRANSMITTER

NEURON

SNRIs, GENERAL

DRUGS & DOSAGES - VENLAFAXINE 75- 300mg po mane - DULOXETINE 60 - 120mg po mane

MOSTLY 2ND LINE TREATMENT FOR MDD

MOST COMMON SIDE-EFFECTS - GASTROINTESTINAL DISCOMFORT - SEXUAL DYSFUNCTION - SEDATION - HYPOTENSION & TACHYCARDIA

FOR TREATMENT AUGMENTATION, TREATMENT RESISTANT MDD & MDD WITH PROMINENT PAIN SYMPTOMS

- DRY MOUTH

NRIs, MECHANISM OF ACTION

PRESYNAPTIC

MAO / COMT

POSTSYNAPTICSYNAPSE

EFFECT

RECEPTOR

NEUROTRANSMITTER

NEURON

NRIs, GENERAL

DRUGS & DOSAGES - REBOXETINE 4 - 5mg po bd

MOSTLY INEFFECTIVE AS AN ANTIDEPRESSANT

MOST COMMON SIDE-EFFECTS - URINARY HESITANCY - CONSTIPATION

- NASAL CONGESTION - PERSPIRATION

FOR AUGMENTATION TREATMENT IN MDD

- DRY MOUTH

- HEADACHE

- DIZZINESS - DECREASED LIBIDO - INSOMNIA

NDRIs, MECHANISM OF ACTION

PRESYNAPTIC

MAO / COMT

POSTSYNAPTICSYNAPSE

EFFECT

RECEPTOR

NEUROTRANSMITTER

NEURON

NDRIs, GENERAL

DRUGS & DOSAGES - BUPROPION 150 - 300mg po mane ( can also be used for smoking cessation)

MOSTLY 2ND LINE ANTIDEPRESSANT

MOST COMMON SIDE-EFFECTS

- NAUSEA

FOR TREATMENT AUGMENTATION, MDD WITH PROMINENT HYPERSOMNIA & FATIGUE OR PATIENTS WITH SEXUAL DYSFUNCTION ON OTHER ANTIDEPRESSANTS

- HEADACHE - INSOMNIA

TADs & TTADs, MECHANISM OF ACTION

PRESYNAPTIC

MAO / COMT

POSTSYNAPTICSYNAPSE

EFFECT

RECEPTOR

NEUROTRANSMITTER

NEURON

TADs & TTADs, GENERAL

TADs - AMITRIPTYLINE 30 - 200mg po nocte

MOSTLY 2ND LINE ANTIDEPRESSANTS DUE TO LESS TOLERABLE SIDE-EFFECTS & RISK OF LETHAL ARRHYTHMIA WITH OVERDOSE

MOST COMMON SIDE-EFFECTS

- ORTHOSTATIC HYPOTENSION

- ANTICHOLINERGIC SIDE – EFFECTS, OFTEN SEVERE (CONSTIPATION, URINARY RETENTION,

- SEDATION

EFFECTIVE ANTIDEPRESSANTS

- CLOMIPRAMINE 10 - 250mg po nocte - IMIPRAMINE 10 - 200mg po nocte - TRIMIPRAMINE 30 - 300mg po nocte - LOFEPRAMINE 140 - 210mg po nocte (mostly used currently)

TTADs - MAPROTILINE 75 - 200mg po nocte (hardly used currently)

DRY MOUTH, BLURRED VISION)

- CARDIAC ARRHYTHMIAS WHICH CAN BE LETHAL IN OVERDOSES (MORE WITH TADs)

MAOIs & RIMAs, MECHANISM OF ACTION

PRESYNAPTIC

MAO / COMT

POSTSYNAPTICSYNAPSE

EFFECT

RECEPTOR

NEUROTRANSMITTER

NEURON

MAOIs & RIMAs, GENERAL

MAOIs - TRANYLCIPROMINE 5 - 100mg po bd

POWERFUL ANTIDEPRESSANTS NOT FOR 1ST LINE TREATMENT

MOST COMMON SIDE-EFFECTS - ORTHOSTATIC HYPOTENSION - INSOMNIA

TYRAMINE-INDUCED HYPERTENSIVE CRISIS

RIMAs - MOCLOBEMIDE 75 - 300mg po bd

- CAUSED BY INTAKE OF TYRAMINE – CONTAINING FOODS WHILST ON THE

- WEIGHT GAIN - OEDEMA - SEXUAL DYSFUNCTION

- SUCH FOODS MUST BE AVOIDED, THESE INCLUDE AGED CHEESES, FISH, BILTONG, MARMITE, SAUERKRAUT, BEER, CHIATI WINE, LIQUEUR

MEDICATION

NASSAs, MECHANISM OF ACTION

PRESYNAPTIC

MAO / COMT

POSTSYNAPTICSYNAPSE

EFFECT

RECEPTOR

NEUROTRANSMITTER

NEURON

NASSAs, GENERAL

CAN BE USED AS 1ST / 2ND LINE TREATMENT, OR IN AUGMENTATION TREATMENT OF MDD

MOST COMMON SIDE-EFFECTS - SEDATION

- INCREASED APPETITE

- MIRTAZAPINE 15 - 45mg po nocte

- WEIGHT GAIN

- DRY MOUTH

DRUGS & DOSAGES

OFTEN USED IN TREATMENT OF MDD WITH PROMINENT INSOMNIA

SARIs, MECHANISM OF ACTION

PRESYNAPTIC

MAO / COMT

POSTSYNAPTICSYNAPSE

EFFECT

RECEPTOR

NEUROTRANSMITTER

NEURON

SARIs, GENERAL

NOT 1ST LINE TREATMENT IN MDD

MOST COMMON SIDE-EFFECTS - SEDATION

- NAUSEA

- TRAZODONE 75 - 300mg po bd

- HEADACHE - DIZZINESS

DRUGS & DOSAGES

OFTEN USED IN TREATMENT OF MDD WITH PROMINENT INSOMNIA

MOSTLY INEFFECTIVE IN THE TREATMENT OF MDD

- ORTHOSTATIC HYPOTENSION

MAs, MECHANISM OF ACTION

PRESYNAPTIC

MAO / COMT

POSTSYNAPTICSYNAPSE

EFFECT

RECEPTOR

NEUROTRANSMITTER

NEURON

22

MAs, GENERAL

NOT 1ST LINE TREATMENT IN MDD

MOST COMMON SIDE-EFFECTS

- NAUSEA

- AGOMELATINE 25-50mg po nocte

- DIZZINESS

DRUGS & DOSAGES

OFTEN USED IN TREATMENT OF MDD WITH PROMINENT INSOMNIA

23

MOOD STABILIZERS

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

CLASSIC MOOD STABILIZER

INDICATIONS

LITHIUM

- 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

- 1ST LINE TREATMENT OPTION IN BIPOLAR DISORDERS (MAINTENACE PHASE)

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

CLASSIC MOOD STABILIZER

MOST COMMON SIDE-EFFECTS

LITHIUM

- WEIGHT GAIN & FLUID RETENTION

- POSTURAL TREMOR

- NAUSEA, VOMITING, DIARRHOEA

- RENAL EFFECTS:

- CARDIAC EFFECTS SECONDARY TO HYPOKALAEMIA:

POLYURIA WITH SECONDARY POLYDIPSIA

T-WAVE FLATTENING OR INVERSION ON ECG

- TERATOGENESIS:

- TREMOR, DYSARTHRIA, ATAXIA

HYPOKALAEMIA RARELY NONSPECIFIC INTERSTITIAL FIBROSIS WITH MORE THAN 10 YEARS OF LITHIUM USE

- BENIGN, USUALLY REVERSIBLE THYROID EFFECTS: MOST COMMONLY HYPOTHYROIDISM HYPERTHYROIDISM GOITER & EXOPHTHALMUS

SINUS DYSRHYTHMIAS, HEART BLOCK, SYNCOPE EPISODES

LITHIUM TOXICITY

CAN CAUSE EBSTEIN’S ANOMALY IN THE UNBORN FETUS OF A PREGNANT MOTHER ON LITHIUM

- 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

CLASSIC MOOD STABILIZER

MONITORING OF THE PATIENT ON LITHIUM

LITHIUM

- CREATININE CLEARANCE (LITHIUM IS EXCRETED EXCLUSIVELY BY THE KIDNEYS, KIDNEY FUNCTION

FOR T-WAVE FLATTENING OR INVERSION, DYSRHYTHMIA/HEART BLOCK)

- FBC (CHECK LEUCOCYTES TO GET A BASELINE VALUE, LITHIUM CAN CAUSE LEUCOCYTOSIS)

- TSH (CHECK FOR HYPO/HYPERTHYROIDISM, LITHIUM CAN INTERFERE WITH THYROID FUNCTION)

- UKE (CHECK POTASSIUM & SIFT FOR KIDNEY DYSFUNCTION)

NEEDS TO BE INTACT)

- ECG (CHECK FOR DYSRHYTHMIA /HEART BLOCK)

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:

- ß-HCG IN FEMALES (LITHIUM IS TERATOGENIC)

- 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 - LITHIUM LEVELS (4 DAYS AFTER STARTING LITHIUM/CHANGING DOSE, THEN

3-6 MONTHLY TO CHECK FOR TOXICITY/SUB-THRESHOLD DOSING/NEED FOR DOSAGE ADJUSTMENT)

ANTICONVULSANTS

DOSAGE - 250-1250mg po bd

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

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)

ANTICONVULSANTS

DOSAGE - STARTING DOSE 200mg po bd, TITRATE UP SLOWLY BY 200mg AT A TIME

CARBAMAZEPINE

INDICATIONS

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)

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)

FOR HYPONATREMIA & SIADH)

- FALLEN OUT OF FAVOUR, NO LONGER ROUTINELY USED, ONLY IN SPECIFIC CASES- SAME USE PROFILE AS VALPROATE BUT SEEMS TO BE LESS EFFECTIVE

- MAINTENANCE DOSE 300-600mg po bd

- INTERFERES WITH THE METABOLISM OF OTHER DRUGS

- UKE (BASELINE BEFORE STARTING TREATMENT THEN PERIODICALLY TO CHECK

- FBC (BASELINE BEFORE STARTING TREATMENT THEN PERIODICALLY TO CHECK TO CHECK FOR BONE MARROW SUPPRESSION)

ANTICONVULSANTS

DOSAGE - STARTING DOSE 25mg po nocte, TITRATE UP SLOWLY BY 25mg EVERY 2 WEEKS TO DECREASE THE

LAMOTRIGINE

INDICATIONS

MOST COMMON SIDE-EFFECTS

- 1ST LINE TREATMENT OPTION FOR PATIENTS WITH PROMINENT BIPOLAR DEPRESSION

- MAINTENANCE DOSE 100-200mg po nocte

- 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

RISK OF STEVENS-JOHNSON SYNDROME

- DIZZINESS & ATAXIA - BLURRED VISION & DIPLOPIA - HEADACHE - SEDATION - NAUSEA & VOMITING - STEVENS-JOHNSON SYNDROME (IF A RASH DEVELOPS, STOP LAMOTRIGINE IMMEDIATELY)

ATYPICAL ANTIPSYCHOTICS

DRUGS & DOSAGE - OLANZAPINE 10-20mg po nocte

INDICATIONS

MOST COMMON SIDE-EFFECTS

- ARIPIPRAZOLE 10-30mg po nocte

MONITORING OF THE PATIENT ON ATYPICAL ANTIPSYCHOTICS- BASELINE FASTING GLUCOSE & LIPOGRAM, BLOOD PRESSURE, WAIST

- QUETIAPINE 300-800mg po nocte

- METABOLIC SYNDROME (MS) – WEIGHT GAIN WITH CENTRAL OBESITY + HYPERTENSION

- 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

+ 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

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

THE END