PHARMACOTHERAPY OF MOOD DISORDERS
DR GIAN LIPPI
CONSULTANT PSYCHIATRIST
UNIVERSITY OF PRETORIA & WESKOPPIES HOSPITAL
FORENSIC UNIT
CONTENTS
BASIC BACKGROUND PHYSIOLOGY
BASICS OF PHARMACOTHERAPY OF MOOD DISORDERS
ANTIDEPRESSANTS (ALL THE CLASSES)
MOOD STABILIZERS (ALL THE CLASSES)
BASIC BACKGROUND PHYSIOLOGY
PRESYNAPTIC
SYNAPSE
POSTSYNAPTIC
MAO / COMT
NEURON
EFFECT
RECEPTOR
NEUROTRANSMITTER
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
ANTIDEPRESSANTS
SSRIs, MECHANISM OF ACTION
PRESYNAPTIC
SYNAPSE
POSTSYNAPTIC
MAO / COMT
NEURON
EFFECT
RECEPTOR
NEUROTRANSMITTER
SSRIs, GENERAL
1ST LINE TREATMENT FOR MDD
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
MOST COMMON SIDE-EFFECTS
-
SEXUAL DYSFUNCTION (DECREASED LIBIDO, ANORGASMIA, erectile dysfunction)
NAUSEA, VOMITING, DIARRHOEA
HEADACHE
INSOMNIA
SNRIs, MECHANISM OF ACTION
PRESYNAPTIC
SYNAPSE
POSTSYNAPTIC
MAO / COMT
NEURON
EFFECT
RECEPTOR
NEUROTRANSMITTER
SNRIs, GENERAL
MOSTLY 2ND LINE TREATMENT FOR MDD
FOR TREATMENT AUGMENTATION, TREATMENT RESISTANT
MDD & MDD WITH PROMINENT PAIN SYMPTOMS
DRUGS & DOSAGES
- VENLAFAXINE 75- 300mg po mane
- DULOXETINE 60 - 120mg po mane
MOST COMMON SIDE-EFFECTS
-
GASTROINTESTINAL DISCOMFORT
SEXUAL DYSFUNCTION
SEDATION
HYPOTENSION & TACHYCARDIA
DRY MOUTH
NRIs, MECHANISM OF ACTION
PRESYNAPTIC
SYNAPSE
POSTSYNAPTIC
MAO / COMT
NEURON
EFFECT
RECEPTOR
NEUROTRANSMITTER
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
NDRIs, MECHANISM OF ACTION
PRESYNAPTIC
SYNAPSE
POSTSYNAPTIC
MAO / COMT
NEURON
EFFECT
RECEPTOR
NEUROTRANSMITTER
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 150 - 300mg po mane ( can also be used for smoking cessation)
MOST COMMON SIDE-EFFECTS
- HEADACHE
- INSOMNIA
- NAUSEA
TADs & TTADs, MECHANISM OF ACTION
PRESYNAPTIC
SYNAPSE
POSTSYNAPTIC
MAO / COMT
NEURON
EFFECT
RECEPTOR
NEUROTRANSMITTER
TADs & TTADs, GENERAL
MOSTLY 2ND LINE ANTIDEPRESSANTS DUE TO LESS
TOLERABLE SIDE-EFFECTS & RISK OF LETHAL ARRHYTHMIA
WITH OVERDOSE
EFFECTIVE ANTIDEPRESSANTS
TADs
-
AMITRIPTYLINE 30 - 200mg po nocte
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)
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)
MAOIs & RIMAs, MECHANISM OF ACTION
PRESYNAPTIC
SYNAPSE
POSTSYNAPTIC
MAO / COMT
NEURON
EFFECT
RECEPTOR
NEUROTRANSMITTER
MAOIs & RIMAs, GENERAL
POWERFUL ANTIDEPRESSANTS NOT FOR 1ST LINE TREATMENT
MAOIs
- TRANYLCIPROMINE 5 - 100mg po bd
RIMAs
- MOCLOBEMIDE 75 - 300mg 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
NASSAs, MECHANISM OF ACTION
PRESYNAPTIC
SYNAPSE
POSTSYNAPTIC
MAO / COMT
NEURON
EFFECT
RECEPTOR
NEUROTRANSMITTER
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 15 - 45mg po nocte
MOST COMMON SIDE-EFFECTS
-
SEDATION
WEIGHT GAIN
INCREASED APPETITE
DRY MOUTH
SARIs, MECHANISM OF ACTION
PRESYNAPTIC
SYNAPSE
POSTSYNAPTIC
MAO / COMT
NEURON
EFFECT
RECEPTOR
NEUROTRANSMITTER
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 75 - 300mg po bd
MOST COMMON SIDE-EFFECTS
-
SEDATION
ORTHOSTATIC HYPOTENSION
DIZZINESS
HEADACHE
NAUSEA
MAs, MECHANISM OF ACTION
PRESYNAPTIC
SYNAPSE
POSTSYNAPTIC
MAO / COMT
NEURON
EFFECT
RECEPTOR
NEUROTRANSMITTER
22
MAs, GENERAL
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
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
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
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
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)
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
- 250-1250mg 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)
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 300-600mg 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)
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 100-200mg 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)
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 1 ST LINE
DRUGS & DOSAGE
- OLANZAPINE 10-20mg po nocte
- QUETIAPINE 300-800mg 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
THE END