SSRIs (Selective serotonin reuptake inhibitors)
GENERAL DESCRIPTION
SSRIs are the drugs used as antidepressants. SSRIs are usually the first choice of treatment for depression because of fewer side effects than other class of antidepressants. SSRIs are generally free of sedative effects and safe in overdose.
| Class | Generic Name | Brand Name |
|
SSRIs (Selective Serotonin reuptake inhibitors) |
Citalopram
|
Celexa |
| Escitalopram | Lexapro | |
| Fluoxetine | Prozac | |
| Sertraline | Zoloft | |
| Fluvoxamine | Faverin, Luvox | |
| Paroxetine | Paxil |
MECHANISM OF ACTION
SSRIs work by elevating certain neurotransmitter in the brain. At presynaptic serotonergic neuron, this neuron interact with postsynaptic neuron which have postsynaptic receptors which are 5-HT. Serotonin is synthesized from amino acid tryptophan by serotonergic neurons. These serotonin is stored in vesicles for regulated release.
At presynaptic noradrenergic neuron, this neuron interact with postsynaptic neuron which have postsynaptic receptors which are β and α1. Norepinephrine is synthesized from amino acid tyrosine by noradrenergic neurons and stored in vesicles awaiting regulated release.
When serotonin and NE release from the neuron they stimulate their receptors and at the same time they transported back to their neurons by a process called reuptake. Serotonin is reuptake by serotonin transporter or SERT and norepinephrine is transported back to their neuron by norepinephrine transporter or NET. Once both chemicals reabsorb they partially repacked in synaptic vesicles in partially broken down into inactive metabolites by an enzyme monoamine oxidase or MAO.
As from the name SSRIs described SSRIs selectively inhibit reuptake of serotonin by blocking the SERT which resulted in increased levels of serotonin available to bind postsynaptic 5-HT receptors.
Why antidepressants take so long to produce antidepressants effects:
In the patient with depression G-proteins tend to cluster in the patches of brain cell membrane rich in cholesterol called lipid raft when stuck on these rafts G protein lack access to molecule called cyclic AMP which is necessary to work and transmit signals of serotonin however later on it was discovered that SSRIs also tend to build up in these lipids rafts which resulted in gradual movement of G proteins out of the rafts toward regions of membrane where they are able to function better.
PHARMACOKINETICS
All SSRIs are orally active. Fluoxetine is notable for the long half-life of its active metabolite, norfluoxetine, 7-9 days at steady state. This long half-life allowed for once weekly dosing. Citalopram and fluvoxamine resemble fluoxetine. SSRIs have 50-90% bioavailability. The metabolism of most antidepressant is facilitated by hepatic CYPs system mostly by CYP2D6.
INDICATIONS
Depression
Generalized anxiety
Post-traumatic stress disorder
Obsessive compulsive disorder
Premenstrual dysphoric disorder
Bulimia nervosa
CONTRAINDICATIONS
SSRIs must not take with pain killers specially aspirin, naproxen, ibuprofen
Hepatic failure
Renal failure
Epilepsy
Manic phase
Lithium, MAOIs, Tryptophan
SIDE EFFECTS & ADVERSE EFFECTS
Manic episodes
Decrease libido
Weight gain
Insomnia
Increase in anxiety
Irritability
Sexual side effects include erectile dysfunction
Nausea
Vomiting
Diarrhea
Abrupt with drawl may cause temporary deficiency of serotonin which may lead to headache, nausea, vomiting, agitation, sleep disturbance.
Serotonin syndrome
DRUG INTERACTION
Nefazodone may cause acute hypotension and weakness when given with fluoxetine.
Nefazodone is contraindicated with other serotogenic antidepressants.
Cyproheptadine may cause oppose the antidepressant effect of fluoxetine.
Cocaine and citalopram may cause multiple drug intoxication.
Dextromethorphan may cause serotonin syndrome or hallucination when given with paroxetine or citalopram.
Grape juice can increase the plasma levels and may cause serotonin like syndrome when given with sertraline or fluoxetine.
When paroxetine and sertraline given with ondansetron and dolasetron respectively, may cause serotonin syndrome.
Interferon may reversed the antidepressant effects of paroxetine.
Clarithromycin may cause acute fluoxetine toxicity when given concurrently and erythromycin my cause serotonin syndrome when given with sertraline.
Serotonin syndrome may cause when metoclopramide, efavirenz, hydromorphone, oxycodone, pentazocine, pethidine, tramadol, morphine given with SSRIs.
SSRIs may increase the plasma level of protease inhibitors like, ritonavir.
Rifampicin decrease the efficacy of citalopram and sertraline.
Methylphenidate may cause delirium or seizure when given with sertraline. Schizophrenia and amphetamine toxicity may cause when fluoxetine is given concurrently.
Tryptophan may cause central and peripheral toxicity when given with fluoxetine.
Paroxetine when given with barbiturates may cause hepatotoxicity.
NURSING INTERVENTIONS:
Enquire the complete health history of the patient including allergy, drug interactions, and family background of depression
Check lab test for CBC, blood glucose, BUN, creatinine, platelets, electrolytes, LFT
Check and identify if any neurological disorder like seizure etc.
Monitor blood pressure and pulse before and during treatment
Administer medicine at night or bed time to avoid drowsiness at day time
Observe mood swing during the treatment
Observe s/s for serotonin syndrome, if any
Observe cardiovascular or neurologic s/s for any disorder, if any
Avoid to administer MAOIs with tyramine containing food
Observe sleep-wake cycle of the patients.
PATIENT EDUCATION
Advise to take medicine at night or bed time to avoid drowsiness at day time and take morning dose early to avoid insomnia.
Advise patient not to discontinue treatment because it may take 2-4 weeks to start antidepressant effects
Inform the patients about the possible side effects of medication specially serotonin syndrome which may be life threatening.
Report immediately if feeling bradycardia, urinary retention, blurred vision, chest pain, and diaphoresis.
Advice to take care and slow change of posture due to dizziness and danger of fall or injuries.
Avoid driving if feeling drowsiness or dizziness.
Do not breast breast feed while taking medicine.