1. PHARMACOTHERAPY OF MOOD DISORDERS
DR GIAN LIPPI
CONSULTANT PSYCHIATRIST
UNIVERSITY OF PRETORIA & WESKOPPIES HOSPITAL
FORENSIC UNIT

2. CONTENTS BASIC BACKGROUND PHYSIOLOGY
BASICS OF PHARMACOTHERAPY OF MOOD DISORDERS
ANTIDEPRESSANTS (ALL THE CLASSES)
MOOD STABILIZERS (ALL THE CLASSES)

3. BASIC BACKGROUND PHYSIOLOGY
PRESYNAPTIC
SYNAPSE
POSTSYNAPTIC
MAO / COMT
NEURON
EFFECT
RECEPTOR
NEUROTRANSMITTER

4. 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

5. ANTIDEPRESSANTS

6. SSRIs, MECHANISM OF ACTION
PRESYNAPTIC
SYNAPSE
POSTSYNAPTIC
MAO / COMT
NEURON
EFFECT
RECEPTOR
NEUROTRANSMITTER

7. 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

8. SNRIs, MECHANISM OF ACTION
PRESYNAPTIC
SYNAPSE
POSTSYNAPTIC
MAO / COMT
NEURON
EFFECT
RECEPTOR
NEUROTRANSMITTER

9. 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

10. NRIs, MECHANISM OF ACTION
PRESYNAPTIC
SYNAPSE
POSTSYNAPTIC
MAO / COMT
NEURON
EFFECT
RECEPTOR
NEUROTRANSMITTER

11. 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

12. NDRIs, MECHANISM OF ACTION
PRESYNAPTIC
SYNAPSE
POSTSYNAPTIC
MAO / COMT
NEURON
EFFECT
RECEPTOR
NEUROTRANSMITTER

13. 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

14. TADs & TTADs, MECHANISM OF ACTION
PRESYNAPTIC
SYNAPSE
POSTSYNAPTIC
MAO / COMT
NEURON
EFFECT
RECEPTOR
NEUROTRANSMITTER

15. 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)

16. MAOIs & RIMAs, MECHANISM OF ACTION
PRESYNAPTIC
SYNAPSE
POSTSYNAPTIC
MAO / COMT
NEURON
EFFECT
RECEPTOR
NEUROTRANSMITTER

17. 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

18. NASSAs, MECHANISM OF ACTION
PRESYNAPTIC
SYNAPSE
POSTSYNAPTIC
MAO / COMT
NEURON
EFFECT
RECEPTOR
NEUROTRANSMITTER

19. 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

20. SARIs, MECHANISM OF ACTION
PRESYNAPTIC
SYNAPSE
POSTSYNAPTIC
MAO / COMT
NEURON
EFFECT
RECEPTOR
NEUROTRANSMITTER

21. 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

22. MAs, MECHANISM OF ACTION
PRESYNAPTIC
SYNAPSE
POSTSYNAPTIC
MAO / COMT
NEURON
EFFECT
RECEPTOR
NEUROTRANSMITTER 22

23. 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

24. MOOD STABILIZERS

25. 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

26. 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

27. 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

28. 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)

29. 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)

30. 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)

31. 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)

32. 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

33. THE END