1. Fawcett J, Barkin RL. J Clin Psychiatry . 1997; 58(Suppl 6): 32 – 39. 2. O'Reardon JP, Amsterdam JD. Psychiatr Ann 1998; 28: 633 – 640. Approximately 2/3 of patients treated for depression will fail to achieve remission (HAM-D ≤ 7) 2
1. Paykel ES, et al. Psychol Med 1995; 25: 1171 – 1180. Patients were interviewed at 3-monthly intervals according to the Clinical Interview for Depression and HAM-D 17 Rating Scale Depressed patients with unresolved symptoms are 3 times more likely to relapse 1
First 6-12 weeks of treatment - aims at remission (control of symptoms).
Inadequate response is associated with poor prognosis.
2. Continuation Treatment
6 months after full symptom control - to maintain remission status and relapse prevention.
3. Maintenance Treatment
Aims at prevention of recurrence of a further episode of depression.
Indicated when higher risk of these recurrence.
“ maintenance dose”
Treatment aims Complete symptom resolution Return to premorbid functioning (psychosocial, occupational) The maintenance of normality The prevention of recurrence
Limbic System Prefrontal Cortex Locus Coeruleus (NA source) Raphe Nuclei (5-HT source) Amygdala Hippocampus Cooper JR, et al. The Biochemical Basis of Neuropharmacology . 8th ed. New York: Oxford University Press; 2003. Descending 5-HT pathways Descending NA pathways
ACUTE MECHANISM OF ACTION UNDESIRABLE PHARMACOLOGICAL ACTIONS TCAs Anticholinergic; antihistaminic; alpha1 adrenoceptor blockade; direct membrane stabilisation SSRIs Citalopram(Cipromil), Fluoxetine (Prozac), Fluvoxamine(Faverin), Paroxetine(Seroxat), Sertraline (Lustral) 5-HT re uptake inhibition MAOIs Phenelzine(Nardil), Isocarboxazid(Marplan) Tranylcypromine(Parnate) Inhibition of MAO-A and MAO-B isoenzymes Interaction with tyramine and sympathomimetic drugs; Irreversible and non-selective inhibition of MAO isoenzymes RIMAs Moclobemide(Manerix) Reversible Inhibition of MAO-A SNRIs Venlafaxine(Efexor) Duloxetine(Cymbalta) 5-HT and NA re uptake inhibition Reboxetine(Edronax) NA re uptake inhibition Mirtazapine(Zispin) Alpha2 adrenoceptor blockade 5-HT2 receptor blockade
CYP2 D6 polymorphism- autosomal recessive trait (slow or ultra-rapid metabolisers)
- Induction of mania/mixed states
- Cycle acceleration (rapid cycling)
- Uncertainty about duration of Rx
Choice of medication
Severity of illness
Previous response to treatment
The likely tolerability of potential side effects
The likely benefit of potential side effects such as sedation
The likely drawbacks of potential side effects such as sedation (i.e. working with machinery, driving etc)
Pregnancy or breastfeeding
Concomitant treatment of physical illness or other psychiatric disorders with the potential for pharmacokinetic/pharmacodynamic interactions.
The presence of relevant physical (for example cardiovascular) disease
Adequate information about the nature of their illness and the need for treatment.
A positive message about the treatability
Explain that antidepressants are not addictive, do not alter one’s personality nor affect their intelligence .
It may take about 2 -4 weeks before s/he their symptoms start showing significant improvement
T hey may experience some side effects
A ntidepressant could be changed if they are unable to tolerate the original drug prescribed.
Regular reviews of the patient’s mood state and suicidal risk offers further reassurance and support, helps ensure compliance and allows prompt intervention in the case of any serious worsening of the condition.
Higher risk of QTc prolongation and Torsades de Pointes – iv administration or high doses
Recent recommendation an ECG to be performed prior to Rx
Great variation in pharmacological profile!
In general they have decreased likelihood of extrapyramidal effects or hyperprolactinaemia
First generation Second generation Weight gain Hyperglycaemia, diabetes Insulin resistance Cardiovascular dis Dyslipidaemia Less EPS Less QT prolongation Less hyperprolactinaemia Neurological side effects EPS Tardive dyskinesia Hyperprolactinaemia
Schizophrenia, other psychoses and any psychotic symptoms
sometimes useful as sedatives
Obsessive compulsive disorder
Drug treatment needs to be tailored to the individual
The aim is to achieve full symptom control
Return to pre morbid functioning
Minimize side effects, ensure safety
Monitor progress over time as mental illnesses are long term relapsing conditions