1. Weight gain with
psychotropic drugs
By
Dr Mohammud Ibraheem

2. Mechanism
1.5HT2A/2C
antagonism
2.Antihistaminic
effects
3.Insulin resistance

3. Serotonergic Receptors
Serotonin receptors are 7 types, 5-HT1
through 5-HT7. Each type can have
subtypes (A, B, etc.).
They are localized in the brain and in
peripheral organs. The majority of 5-HT
receptors are postsynaptic.
5-HT1A and 5-HT1B are mainly presynaptic
Serotonin receptors are coupled to G
proteins except 5-HT3 receptors which are
ion channel.

4. Sites of 5-HT2A receptors
5-HT2A receptors are found in::
1. High density in the claustrum
2. Limbic system (amygdala and
hippocampus)
3. The basal ganglia

5. 5HT2A
Agonist Antagonists
1. Efavirenz (an
antiretroviral drug)
2. Lisuride (an
antiparkinson dopamine
agonist)
3. Mefloquine (an
antimalarial drug)
4. lorcaserin
5. lumateperone
1. Trazodone
2. Tricyclic antidepressants:
Amitriptyline, Nortriptyline,
Amoxapine, Clomipramine,
Doxepin, Maprotiline, Imipramine
3. Tetracyclic antidepressants:
Mianserin, Mirtazapine
4. Ketanserin
5. Antipsychotics ; Cariprazine,
clozapine, olanzapine, quetiapine,
risperidone, brexpiprazole,
asenapine, haloperidol and
chlorpromazine
6. Cyproheptadine

6. Sites of 5HT2C receptors
5HT2C receptors are expressed in:
1) The nucleus accumbens
2) Caudate putamen
3) Olfactory tubercle
4) Claustrum, cingular cortex, amygdala
5) Dentate gyrus, periaqueductal gray,
entorhinal cortex, some brainstem motor
nuclei

7. 5HT2C
Agonists Antagonists
1. Fenfluramine (Dravet
syndrome and Lennox–
Gastaut syndrome)
2. Lorcaserin
3. Arpiprazole ( partial
agonist)
1. Agomelatine
2. Flibanserin (pre-
menopausal hypoactive
sexual desire disorder)
3. Fluoxetine
4. Mirtazapine
5. Trazodone

8. H1 antagonisms
a) Tricyclic antidepressants;; DOXEPIN the
most potent antihistaminic, the second
potent is amitrptalin, the less potent is
desipramine.
b) Mirtazepine
c) Mianserin
d) Antipsychotics; Ziprasidone, risperidone,
olanzapine, clonzapine, iloperidone and
cariprazine

9. Insulin resistance
I. Antipsychotics; olanzapine, clozapine,
risperidone, qutiapine, ziprasidone,
arpiprazole
II. Mood stabilizers; valporic acide

10. Low potency antipsychotics
(chlorpromazine and
thioridazine) produce more
weight gain and sedation
than high potency agents
(haloperidol and
fluphenazine).

11. Mean weight increases during the first year
of therapy
1. 12 to 14lb for clozapine (5 to 6 kg)
2. 15 to 26lb for olanzapine (7 to 12kg)
3. 6 to 12lb for quetiapine (2.5 to 5kg)
4. Up to 5lb for risperidone (2 to 2.5kg)
5. Less than 2lb for Ziprasidone and
aripiprazole

12. Thank you