1. Antidepressants
The optimal use of antidepressant required a clear understanding of their mechanism of action, pharmacokinetics, potential drug interaction and the deferential diagnosis of psychiatric illnesses. Dr Malek Zihlif

2. A World Health Organization (WHO) Prediction
Depression
A World Health Organization (WHO) Prediction
Depression is currently the FOURTH most significant cause of suffering and disability worldwide
and, sadly, It will be the SECOND most debilitating human condition by the year (1st is cardiovascular diseases)
In USA,10% of females are depressed and 5%of males (Lucky). Also in Jordan female are depressed more than males (psychological and endocrine issues)
E.g. during pregnancy, postpartum depression or if she give birth to twin
It is a growing problem
But men have more psychosis (schizophrenia) than women.

3. Chemical “Jobs” Dopamine Attention Pleasure Emotions Reward Motivation
Movement
Norepinephrine
alertness
Observance
Daydreaming
Heart/BP rates
Stress
Serotonin
Regulates mood
sleep
emesis
sexuality
Appetite
impulsiveness/ aggression

4. Depression 2 types of Depression: Mild: we use psychotherapy
Major: we have to use drugs
Bipolar: sometimes overactive, other times depressed
2ry depression: after social shock (death , divorce,…etc)>>>اذا حكيتله نكتة بضحك>>>Tx: behavioral, sometimes drugs for 6 months
Neurotransmitter Depression: genetically (شوه ما عملتله ما بضحك)>>>Tx: life-long drugs therapy
Symptoms
Cognitive>>>Thoughts of hopelessness, poor confidence, negative thoughts (more toward suicide).
Emotional>>>Feeling sad, unable to feel pleasure, irritability
Psychomotor/Physical
Decreased libido, energy
Sleep changes (70% less, 30% more)
Appetite changes (70 % less, 30 % more)
We can not treat all patients with same drug

5. Depression: Treatment
Just tell the patient that you are here to help him
Antidepressant Medications
Selective serotonin reuptake inhibitor (SSRI’s) are first line of treatment
Psychotherapy
Usually individual psychotherapy
Cognitive behavioral therapy has most evidence for efficacy of treatment.
Sometimes exercise or body awareness has been found to helpful
من حسنات الزواج: high level of serotonin

6. Zoloft: most prescribed drug

8. MONOAMINE OXIDASE (MAO) AND DEPRESSION
MAO catalyze deamination of intracellular monoamines
MAO-A oxidizes epinephrine, norepinephrine, serotonin
MAO-B oxidizes phenylethylamine
Both oxidize dopamine nonpreferentially
MAO transporters reuptake extracellular monoamine

10. Monoamine oxidase inhibitors (MAOI)
Inhibition of intra-neuronal degradation of serotonin and norepinephrine causes an increase in extracellular amine levels.
Phenelzine is a none selective مهم (with tyramine intake>>>BP problems)
Selegiline is a selective for MAO-B) مهم
Side effects: (may be similar to the symptoms of the disease)
Blood pressure problems, Dietary requirements, Weight gain, Insomnia, Edema.
Last drug choice (20% which not respond to other drugs)

11. Tricycle antidepressant (Amitriptyline)
TCAs inhibit serotonin, norepinephrine, and dopamine transporters, slowing reuptake. (selective more to NE and serotonine)
with a resultant increase in activity.
Muscarinic acetylcholine receptors, alpha-adrenoceptors, and certain histamine (H1) receptors are blocked.
Side effects:
drug-induced Sedation (H1)
Orthostatic hypotension (alpha)
(2) Cardiac effects
(3) Anticholinergeric effects dry mouth, constipation, blurred vision, urinary retention (atropine-like effect)
We select the drug depending on the side effects not the efficacy
Last choice drugs (Imipramine)>>>used before MAOIs
All antidepressants need 2-6 weeks for the effect to appear….why? Adaptation mechanisms (feedback inhibition to the release of serotonin) the after 2-6 wks of Tx>>>they undergo desensitization or downregulation
Do not start with very strong drugs>>>may lead to mania

12. SSRIs (Serotonin-specific reuptake inhibitors)
inhibits the reuptake of serotonin without seriously effecting the reuptake of dopamine & norepinephrine.
Most common side effects include GI upset, sexual dysfunction (30%+!), anxiety, restlessness, nervousness, insomnia, fatigue or sedation, dizziness>>> will be tolerated
Can develop a discontinuation syndrome with agitation, nausea, disequilibrium and dysphoria except for Fluxetine (accumilation in the body>>>sustained release)

13. SSRI/SNRI Discontinuation Syndrome in Adults
F.I.N.I.S.H.حفظ
Flu-like symptoms: fatigue, muscle aches, headache, diarrhea
Insomnia: vivid or disturbing dreams
Nausea
Imbalance: gait instability, dizziness, lightheadedness, vertigo
Sensory disturbance: paresthesia, “electric shock” sensation, visual disturbance
Hyperarousal: anxiety, agitation
Onset: hours + Resolution: 1-14 days
Incidence: ~ % (who have been treated at least 6 weeks)
Tapering is needed >>>for 6 months to 1 year
DISCONTINUATION SYNDROME COMMONLY SEEN WHEN WOMEN FINDS OUT SHE’S PREGNANT AND STOPS HER MEDICATION – Not likely to occur with Prozac because of it’s long half life

14. Why there are many of them
Paroxetine: Sedating properties (dose at night) offers good initial relief from anxiety and insomnia
Significant CYP2D6 inhibition
Sertraline: Increased number of GI adverse drug reactions
Fluoxetine Secondary to long half life, less Discontinuation Syndrome
Significant P450 interactions so this may not be a good choice in pts already on a number of meds
Initial activation may increase anxiety and insomnia
More likely to induce mania than some of the other SSRIs

15. Serotonin/Norepinephrine reuptake inhibitors (SNRIs)
Slightly greater efficacy than SSRIs
Slightly fewer adverse effects than SSRIs
Venlafaxine
Duloxetine
1. Can cause a mmHG dose dependent increase in diastolic BP.
2. May cause significant nausea,
3. Can cause a bad discontinuation syndrome, and taper recommended after 2 weeks of administration
Venlafaxine is a racemix mixture
While SSRIs are less potent than the other classes of drugs, they have more manageable side effects so they’re considered better
The mechanism is similar to SSRIs, as are the side effects. However, the rate of suicide for SNRIs has been debateable, especially venlafaxine.
Finnish study showed Ven increased suicide risk 1.6 times compared to no treatment while Fluoxetine halved it.
FDA study showed 5-fold increase in <25 so it is contraindicated in adolescents.

16. Buproprion Good for use as an augmenting agent Add on drug
Mechanism of action likely reuptake inhibition of dopamine and norepinephrine
No weight gain, no sexual side effects, no sedation nor cardiac interactions
Low induction of mania
Does not treat anxiety unlike many other antidepressants and can actually cause anxiety, agitation and insomnia

18. Following the initiation of the antidepressant drug treatment there is generally a therapeutic lag lasting for 3-4 weeks.
8 weeks trial, then you allow to switch to another antidepressant.
Partial response then add one another drug from different class.

19. if the initial treatment was successful then 6-12 maintenance periods.
If the patient has experience two episodes of major depression, then it is advisable to give an anti depressant life long.