⦿ Most clinically useful antidepressant

⦿ The action of SSRIs is by block the ⦿ The adverse effects of SSRIs include:
drugs potentiate, either directly or reuptake of serotonin leading to 1) Sleep disturbances.
indirectly, the actions of: increased conc.s of the NT in the
ANTIDEPRESSANTS synaptic cleft.
2) Sexual dysfunction.
❖ Norepinephrine (NE) and/or 3) Use in children and teenagers(suicidal).
By Dr. Rana Hani
❖ Serotonin (5-HT) in the brain. 4) Overdose: may cause:
➢ Cardiac arrhythmias
➢ Seizures
➢ Serotonin syndrome, include the hyperthermia,
muscle rigidity, sweating, clonic muscle twitching,
and changes in mental status and vital signs.
5) Discontinuation syndrome.

⦿ Antidepressants, 2. Serotonin/Norepinephrine reuptake

⦿ The symptoms of depression are 1.Selective serotonin reuptake inhibitors (SSRIs) including SSRIs inhibitors (SNRIs)
feelings of: ⦿ SSRIs having greater selectivity for the take at least 2 weeks to produce ⦿ They include:
❖ Sadness and serotonin transporter than NE significant improvement in mood, ➢ Venlafaxine,
❖ Hopelessness, transporter.
➢ Desvenlafaxine,
❖ The inability to experience pleasure, ⦿ They have little blocking activity at: ➢ Levomilnacipran, and
❖ Changes in sleep patterns, ❖ Muscarinic, ⦿ and maximum benefit may require ➢ Duloxetine.
❖ Changes in appetite, ❖ α-adrenergic, and up to 12 weeks or more.
❖ Loss of energy, and ❖ Histaminic H1 receptors.
❖ Suicidal thoughts.

⦿ Mania is characterized by the opposite ⦿ The majority of SSRIs have plasma half-lives
⦿ SNRIs effective in treating:
⦿ The SSRIs include:
behavior: that range between 16 and 36 hours. ⦿ Depression in patients in whom SSRIs are
➢ Fluoxetine, ineffective.
➢ Anger,
➢ Citalopram,
➢ Rapid thought and speech patterns, ⦿ Fluoxetine differs by having a much longer ⦿ Depression is often accompanied by chronic
➢ Extreme self-confidence, and ➢ Escitalopram, half-life (50 hours), and the half-life of its active painful symptoms,
➢ Impaired judgment. ➢ Fluvoxamine, metabolite S-nor-fluoxetine is quite long,
averaging 10 days. ⦿ Both SNRIs and the TCAs, with their dual
➢ Paroxetine, and inhibition of both serotonin and NE reuptake,
➢ Sertraline. are effective in relieving pain associated with
diabetic peripheral neuropathy, and low back
pain.

3. Atypical antidepressants D. Vilazodone ⦿ Mechanism of action ⦿ The adverse effects of TCAs:

⦿ They are a mixed group of agents that have ⦿ It is a serotonin reuptake inhibitor and a 5-HT1a 1. Inhibition of neurotransmitter reuptake. a. By block of muscarinic receptors leads
actions at several different sites, includes: partial agonist, but to unknown extent. 2. Blocking of receptors: TCAs also block to:
✓ Serotonergic, ✓ Blurred vision,
A. Bupropion ✓ α-adrenergic, ✓ Dry mouth,
➢ It is a weak dopamine and NE reuptake ✓ Histaminic, and ✓ Urinary retention,
inhibitor that is used to: ✓ Muscarinic receptors. ✓ Tachycardia,
✓ Alleviate the symptoms of depression. ✓ Constipation, and
✓ Decreasing withdrawal symptoms of nicotine Amoxapine also blocks ✓ Aggravation of angle-closure glaucoma.
in patients trying to quit smoking. ✓ 5-HT2 and ✓ Arrhythmias in an overdose.
✓ Dopamine D2 receptors.

B. Mirtazapine E. Vortioxetine ⦿ The TCAs b. By block α-adrenergic receptors,

⦿ It enhances serotonin and norepinephrine ⦿ It utilizes a combination of: ❑ Elevate mood, causing:
neurotransmission by serving as an antagonist ❖ Serotonin reuptake inhibition, ✓ Hypotension,
❑ Improve mental alertness,
at presynaptic α2 receptors. ❖ 5-HT1a agonism, and
❑ Increase physical activity. ✓ Dizziness, and
❖ 5-HT3 and 5-HT7 antagonism, ✓ Reflex tachycardia.
⦿ Antagonism at 5-HT2 receptors sedation. but unclear to what extent.
⦿ The onset of the mood elevation is slow,
requiring 2 weeks or longer. c. By block histamine H1 receptors
causing sedation.

⦿ The TCAs are effective in

C. Nefazodone and trazodone
⦿ Weak inhibitors of serotonin reuptake.
⦿ Their therapeutic benefit due to their
ability to block postsynaptic 5-HT2a
receptors.
⦿ So they are sedating agent,
4. Tricyclic antidepressants (TCAs)
⦿ The TCAs block NE and serotonin reuptake into
the presynaptic neuron which have different
adverse effects from SNRIs.
⦿ The TCAs include the:
a. Tertiary amines imipramine, amitriptyline,
clomipramine, doxepin, and trimipramine.
b. Secondary amines desipramine and nor-
triptyline and pro-triptyline.
c. “Tetracyclic” antidepressant agents, maprotiline
and amoxapine, which are commonly included in
the general class of TCAs.
⦿ Also it cause:
❖ Treating moderate to severe depression.
❖ Weight gain
❖ Patients with panic disorder. ❖ Sexual dysfunction (in a minority of patients).
❖ Imipramine has been used to control bed-
wetting in children older than 6 years of age. ⦿ The TCAs have a narrow therapeutic index.
❖ Used to prevent migraine headache.
❖ Treat chronic pain syndromes of unkomn
cause.
❖ Low doses of TCAs, especially doxepin, can
be used to treat insomnia.

5. Monoamine oxidase inhibitors (MAO)
⦿ MAO is a mitochondrial enzyme found in nerve
and other tissues, such as the gut and liver.
⦿ In the neuron, MAO functions as a “safety
valve” to oxidatively deaminate and inactivate
any excess NTs (NE, dopamine, and
serotonin).
⦿ Most MAOIs give their action by form ⦿ So they show a high incidence of drug–drug
stable complexes with the enzyme, and drug–food interactions.
causing irreversible inactivation.
⦿ The antidepressant action of MAOs is delayed
several weeks.
⦿ increased stores of NE, serotonin, and
dopamine within the neuron
⦿ diffusion of excess NT into the synaptic
space.

⦿ The MAOIs may ⦿ These drugs inhibit not only MAO in the brain ⦿ The MAOIs are considered last-line agents in Treatment of mania and bipolar disorder
➢ irreversibly
or inactivate the enzyme, but also MAO in the liver and gut, many treatment settings. ⦿ The medications used for the treatment of mania are:
➢ reversibly A. Lithium
⦿ It salts are used acutely and prophylactically for
⦿ That catalyzes oxidative deamination of drugs ⦿ The use of MAOIs with other antidepressants managing bipolar patients.
and potentially toxic substances, such as is contraindicated.
permitting NTs to escape degradation tyramine, which is found in certain foods. ⦿ Many cellular processes are altered, but the mode of
action is unknown.
⦿ The antidepressants require a washout period
of at least 2 weeks before the other type is ⦿ The therapeutic index of lithium is extremely low, and
accumulate within the presynaptic neuron administered, with the exception of fluoxetine, lithium salts can be toxic.
⦿ Tyramine causes the release of large amounts
of stored catecholamines from nerve which should be discontinued at least 6
weeks. ⦿ Thyroid function may be decreased and should be
terminals, monitored.
leak into the synaptic space.

⦿ The four MAOIs include: ⦿ Resulting in a hypertensive, with signs and B. Other drugs
symptoms such as: ⦿ Several antiepileptic drugs have been approved
➢ Phenelzine,
❖ Headache, as mood stabilizers for bipolar disorder,
➢ Tranyl-cypromine, including:
➢ Iso-carboxazid, and
❖ Stiff neck, ➢ Carbamazepine,
➢ Selegiline.
❖ Tachycardia, ➢ Valproic acid, and
❖ Nausea, ➢ Lamotrigine,
⦿ Use of MAOIs is limited due to the ❖ Hypertension,
complicated dietary restrictions required while ❖ Cardiac arrhythmias, ⦿ Also newer antipsychotics as:
taking these agents. ❖ Seizures, and, ➢ Quetiapine,
❖ Stroke. ➢ Lurasidone, and
➢ The combination of olanzapine and fluoxetine.

⦿ Agents that may improve manic symptoms

include:
➢ Chlorpromazine and
➢ Haloperidol

⦿ Newer antipsychotics.
➢ Risperidone,
➢ Olanzapine,
➢ Ziprasidone,
➢ Aripiprazole,
➢ Asenapine, and
➢ Quetiapine.

Thank you