antidepressants · •tricyclic antidepressants are not merely antidepressants, since one of them...
TRANSCRIPT
![Page 1: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/1.jpg)
Antidepressants
Dr. Layali Abbasi Psychiatrist
Al-Balqa Applied University
5th year/Faculty of Medicine 2019-2020
![Page 2: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/2.jpg)
• Selective Serotonin Reuptake Inhibitors(SSRIs)
• Serotonin and Norepinephrine Reuptake Inhibitors(SNRIs)
• Tricyclic and tetracyclic antidepressants (TCAs)
• Bupropion
• Mirtazapine
![Page 3: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/3.jpg)
SSRIs
• Paroxetine
• Fluoxetine
• Fluvoxamine
• Sertraline
• Citalopram
• Escitalopram
![Page 4: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/4.jpg)
The Mechanism of Action of SSRIs
• Antidepressant effects are generally not seen
until 2 to 4 weeks of continuous treatment.
• The role of 5HT1A receptor downregulation in the mechanism of action of SSRIs.
![Page 5: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/5.jpg)
This image shows a serotonergic neuron. We can see the somatodendritic region, the axon and the presynaptic terminal. Here is also depicted a postsynaptic neuron that is stimulated by the serotonergic neuron
![Page 6: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/6.jpg)
There are 14 subtypes of serotonin receptors, the 5HT1A is one of them. When this receptor is stimulated it inhibits firing of serotonergic neurons, this means that it works as an autoreceptor that inhibits serotonergic activity.
![Page 7: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/7.jpg)
Here 5HT1A receptors are expressed in the somatodendritic region of a serotonergic neuron. This picture is a schematic representation that emphasizes the role of 5HT1A receptors as inhibitory autoreceptors.
![Page 8: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/8.jpg)
The serotonin transporter (SERT) is a monoamine transporter protein. This is a membrane protein that transports serotonin from synaptic spaces into presynaptic neurons
![Page 9: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/9.jpg)
Selective serotonin reuptake inhibitors and other antidepressants block the SERT transporter. The result is an increased availability of serotonin in the synaptic space.
![Page 10: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/10.jpg)
If you pay attention there is an important difference with the previous slides: there are less 5HT1A receptors, this is, 5HT1A receptors are downregulated. As a response to serotonin stimulation, the serotonergic neuron reduces the number of 5HT1A receptors, this phenomenon is known as downregulation. Since downregulation is mediated by genomic mechanisms, the reduction of 5HT1A receptors is not immediate, this occurs in weeks. This has been proposed as a possible explanation of antidepressants' delay in therapeutic effects.
![Page 11: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/11.jpg)
Since there are less 5HT1A receptors expressed in the somatodendritic region, the neuron is now disinhibited. As a consequence, firing rate is increased. This in turn increases serotonin release to the synaptic space, which stimulates postsynaptic serotonin receptors. In summary, inhibition of serotonin reuptake increases serotonin concentration, which causes a downregulation of 5HT1A receptors. After the number of 5HT1A receptors is reduced, the neuron is disinhibited to release more serotonin in the synaptic space.
![Page 12: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/12.jpg)
Side effects of SSRIs
![Page 13: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/13.jpg)
![Page 14: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/14.jpg)
![Page 15: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/15.jpg)
![Page 16: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/16.jpg)
![Page 17: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/17.jpg)
![Page 18: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/18.jpg)
![Page 19: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/19.jpg)
Many clinicians see it as suitable for anxious depression
Sexual dysfunction
Discontinuation syndrome
Weight gain
Paroxetine - Overview
![Page 20: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/20.jpg)
Inhibits SERT
Muscarinic blockade: anticholinergic properties.
Potentially problematic in the elderly
At high doses: NET inhibition
Paroxetine Pharmacodynamics
![Page 21: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/21.jpg)
FDA-approved indications for paroxetine
![Page 22: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/22.jpg)
Nausea Headache Somnolence
Dry mouth Sweating
Common side effects
![Page 23: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/23.jpg)
• Sexual dysfunction more problematic with paroxetine than with other SSRIs
• Dose dependent side effect
SSRI-induced sexual dysfunction
![Page 24: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/24.jpg)
Weight gain
• Weight gain needs to be considered when choosing paroxetine
• One of the antidepressants with highest risk of weight gain
![Page 25: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/25.jpg)
Discontinuation syndrome
Discontinuation syndrome with
paroxetine
1/3 of patients after
abrupt cessation
Short half life
No active metabolites
![Page 26: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/26.jpg)
• Paroxetine is labeled as pregnancy risk category D (this means that there is positive evidence or risk to human fetus).
![Page 27: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/27.jpg)
Fluoxetine - Overview
First AD of the SSRI class
Activating properties
Long half-life / Weekly capsule
Potent CYP2D6 inhibitor
![Page 28: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/28.jpg)
Fluoxetine
• Fluoxetine has activating properties that make
it a good option for patients with retarded depression or atypical depression. However, we should avoid activation in patients with insomnia and agitation.
![Page 29: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/29.jpg)
Fluoxetine
![Page 30: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/30.jpg)
![Page 31: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/31.jpg)
![Page 32: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/32.jpg)
Fluoxetine
![Page 33: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/33.jpg)
Fluvoxamine
![Page 34: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/34.jpg)
Fluvoxamine
![Page 35: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/35.jpg)
Fluvoxamine
![Page 36: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/36.jpg)
Major depressive disorder
Panic disorder
Premenstrual dysphoric disorder
Posttraumatic stress disorder
Social anxiety disorder
Obsessive compulsive disorder
Sertraline FDA-Approved Indications
![Page 37: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/37.jpg)
Off-label uses
• Depression associated with Parkinson’s disease
• Generalized anxiety disorder
Sertraline
![Page 38: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/38.jpg)
Indication Citalopram Escitalopram
Depression X X
Generalized anxiety disorder
x
FDA-Approved Indications
Citalopram and Escitalopram
![Page 39: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/39.jpg)
• OCD
• Panic disorder
• PTSD
• Social anxiety disorder
• Premenstrual dysphoric disorder
Off-label uses
Citalopram and Escitalopram
![Page 40: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/40.jpg)
• Most common side effects:
– Nausea and vomiting
– Increased sweating
– Dry mouth
– Headache
• Pregnancy category C
Citalopram and Escitalopram
![Page 41: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/41.jpg)
SNRIs
• Venlafaxine and Desvenlafaxine
• Duloxetine
![Page 42: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/42.jpg)
• SNRIs combine the robust SERT inhibition of the SSRIs with various degrees of inhibition of the norepinephrine transporter (or NET).
![Page 43: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/43.jpg)
Venlafaxine
• FDA-approved indications:
-Major depressive disorder
-Generalized anxiety disorder
-Social anxiety disorder
-Panic disorder
![Page 44: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/44.jpg)
Venlafaxine is one of the antidepressants most commonly associated with discontinuation syndrome.
![Page 45: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/45.jpg)
Tricyclic and tetracyclic antidepressants (TCAs)
• Amitriptyline
• Clomipramine
• Imipramine
• Desipramine
• Nortriptyline
![Page 46: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/46.jpg)
Tricyclic and tetracyclic antidepressants (TCAs)
• Block the reuptake pumps for norepinephrine (i.e., NET), or for both norepinephrine and serotonin (i.e., SERT).
• Some tricyclics have equal or greater potency for SERT inhibition (e.g., clomipramine); others are more selective for NET inhibition (e.g., desipramine, maprotiline, nortriptyline, protriptyline).
• Most, however, block both serotonin and norepinephrine reuptake to some extent.
• In addition, some tricyclic antidepressants have antagonist actions at 5HT2A and 5HT2C receptors which could contribute to their therapeutic profile.
![Page 47: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/47.jpg)
• Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them have anti-panic effects at antidepressant doses and efficacy for neuropathic and low back pain at low doses.
![Page 48: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/48.jpg)
Side effects of tricyclic antidepressants (TCAs)
![Page 49: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/49.jpg)
![Page 50: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/50.jpg)
![Page 51: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/51.jpg)
![Page 52: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/52.jpg)
• Because of their side effects and potential for death in overdose, tricyclic antidepressants have fallen into second-line use for depression.
![Page 53: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/53.jpg)
• Contraindications: Absolute contraindications: MI (until 6 months after the MI) Narrow-angle glaucoma Relative contraindications: Cardiac disease ( a baseline ECG is recommended). Prostatic hypertrophy or other obstructive uropathy ( secondary to anti-cholinergic side effects).
![Page 54: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/54.jpg)
Norepinephrine Dopamine Reuptake Inhibitor (NDRI)
Used for depression and smoking cessation
Different side effects profile:
• lack of sexual side effects
• risk of seizures
Bupropion - Overview
![Page 55: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/55.jpg)
Mechanism of Action
• Reuptake inhibition of:
– Norepinephrine transporter (NET)
– Dopamine transporter (DAT)
• MOA may involve the presynaptic release of NE and DA.
![Page 56: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/56.jpg)
Mechanism of Action - Pharmacology
• Non competitive antagonist of nAch receptors
• Might contribute to antidepressant effects as well as effectiveness in smoking cessation
![Page 57: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/57.jpg)
Bupropion for depression
Efficacy comparable to SSRIs and venlafaxine
Effective doses: 150-300 mg/day
Not sedating
•Retarded depression: decreased energy, interest and pleasure
Mildly stimulating properties
![Page 58: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/58.jpg)
Bupropion and sexual side effects
• Sexual dysfunction not a side effect when using bupropion.
![Page 59: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/59.jpg)
Adverse Effects
Lack of anticholinergic, antihistaminic and orthostatic hypotensive effects.
Restlessness Activation Tremors
Insomnia Nausea
![Page 60: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/60.jpg)
Adverse Effects - Seizures
• IR: 0.4% at doses up to 450 mg/day
• SR: 0.1% for doses up to 300 mg/day
Incidence of seizures:
Dose dependent effect
• Screen for seizure disorder or other organic brain conditions
Before prescribing bupropion:
![Page 61: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/61.jpg)
Mirtazapine
![Page 62: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/62.jpg)
Mirtazapine- Overview
NaSSA (Noradrenergic and specific serotonergic antidepressant)
H1 antagonist
Sedation and weight gain
Used in the elderly population
No significant interactions
Used as augmenting agent
![Page 63: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/63.jpg)
Mirtazapine Pharmacology
• No monoamine reuptake inhibition
• Serotonergic and noradrenergic antidepressant
• Antagonist at: • a2
• H1
• 5HT2A, 5HT2C, 5HT3
![Page 64: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/64.jpg)
Mirtazapine: a2 antagonist
a2 receptors – Autoreceptors: noradrenergic neurons
– Heteroreceptors: serotonergic neurons
![Page 65: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/65.jpg)
Mirtazapine blocks a2 presynaptic autoreceptors
a2 presynaptic blockade
Loss of inhibition
Increased NE release
![Page 66: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/66.jpg)
Mirtazapine blocks a2 somatodendritic receptors in 5HT
neurons = activation
![Page 67: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/67.jpg)
Mirtazapine blocks 5HT3 receptors in the CTZ
Kast, R. E., and K. F. Foley. "Cancer chemotherapy and cachexia: mirtazapine
and olanzapine are 5‐HT3 antagonists with good antinausea effects." European Journal of Cancer Care 16.4 (2007): 351-354.
![Page 68: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/68.jpg)
Effects on other 5HT receptors
• Antagonist at:
– 5HT2A
– 5HT2C
Croom, Katherine F., Caroline M. Perry, and Greg L. Plosker. "Mirtazapine.“ CNS drugs 23.5 (2009): 427-452.
![Page 69: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/69.jpg)
FDA-Approved Indications
Indication Dosage range
Depression 15-45 mg/day
Remeron (Mirtazapine) [Prescribing Information] NJ: Merck & Co., Inc. Accessed June 2014
![Page 70: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/70.jpg)
Mirtazapine: tolerability profile
Sedation:
• 50% of patients during first week of treatment
Increased appetite: weight gain
• 15-25% of patients
- Dry mouth - Premarketing studies: agranulocytosis, association not established
![Page 71: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/71.jpg)
Mirtazapine: side effects profile
Significantly lower frequency of:
– Antidepressant-induced sexual dysfunction
– Gastrointestinal disturbances – Insomnia Very low risk of sexual
dysfunction
![Page 72: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/72.jpg)
Antidepressant Discontinuation Syndrome
![Page 73: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/73.jpg)
![Page 74: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/74.jpg)
![Page 75: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/75.jpg)
![Page 76: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/76.jpg)
![Page 77: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/77.jpg)
![Page 78: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/78.jpg)
![Page 79: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/79.jpg)
![Page 80: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/80.jpg)
![Page 81: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/81.jpg)
![Page 82: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/82.jpg)
![Page 83: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/83.jpg)
![Page 84: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/84.jpg)
What to do ? 1. Provide reassurance to the patient • Reversible, not life threatening, will run its course within 1 to 2 weeks. 2. Consider restarting the medication with a slow dose taper • If symptoms occur during tapering: Consider restarting at the original dose and then taper at a slower rate. • If slow tapering is poorly tolerated: Consider substituting with fluoxetine
![Page 85: Antidepressants · •Tricyclic antidepressants are not merely antidepressants, since one of them (clomipramine) has anti-obsessive–compulsive disorder effects and many of them](https://reader034.vdocuments.us/reader034/viewer/2022042605/5f52ae2570481f579760a182/html5/thumbnails/85.jpg)
THE END