Products
The selective serotonin reuptake inhibitors (SSRIs) are mainly taken in the form of film-coated tablets or capsules. In addition, other dosage forms such as dispersible tablets, melting tablets and drops are available. Zimelidin was the first to be developed in the 1970s and was approved in the early 1980s. Sales had to be discontinued due to undesirable effects. The second agent, indalpin, was also soon withdrawn from the market. Fluvoxamine was the third active ingredient to be released, in many countries in 1983. Well-known brand names include Prozac (fluoxetine), Cipralex (escitalopram) and Zoloft (sertraline). Today, numerous generic drugs are also available.
Structure and properties
The older SSRIs are analogs of 1st-generation antihistamines. Zimelidine is derived from brompheniramine and fluoxetine from diphenhydramine. The molecules were rationally developed from the monoamine hypothesis.
Effects
SSRIs (ATC N06AB) have antidepressant and mood-elevating properties. The effects are based on selective inhibition of reuptake of the neurotransmitter serotonin into the presynaptic neuron. This increases the concentration in the synaptic cleft. The drug target is the serotonin transporter SERT. Selectivity primarily relates to comparison with older antidepressants such as the tricyclic antidepressants, which are nonselective.
Indications
Indications include (selection):
- Prevention and treatment of depression
- Panic disorders
- Obsessive-compulsive disorders
- Social phobia
- Bulimia (Bulimia nervosa)
- Generalized anxiety disorders
- Post-traumatic stress disorder
- Premature ejaculation (dapoxetine)
Many other indications exist for which there is currently no regulatory approval.
Dosage
According to the SmPC. For most SSRIs, once-daily dosing is sufficient because of the long half-life. Full effectiveness is usually delayed after two to four weeks.
Abuse
Unlike other centrally acting drugs, SSRIs are not abused as intoxicants.
Active ingredients
- Citalopram (Seropram, generic).
- Dapoxetine (Priligy)
- Escitalopram (Cipralex, generics) is the -enantiomer of citalopram.
- Fluoxetine (Fluctine, generic, USA: Prozac).
- Fluvoxamine (Floxyfral, generic).
- Paroxetine (Deroxat, generics)
- Sertraline (Zoloft, generic)
Closely related representatives are such as trazodone (Trittico) and vortioxetine (Brintellix) are not counted as SSRIs because they are additionally active at serotonin receptors. They are referred to as SARIs.
Contraindications
Full precautions can be found in the drug label. Many SSRIs are contraindicated in combination with MAO inhibitors.
Interactions
Some SSRIs are substrates of CYP450 isozymes, such as fluoxetine of CYP2D6 and sertraline of CYP2D6 and CYP3A4. Combination with CYP inhibitors or CYP inducers may lead to drug-drug interactions. SSRIs may prolong the QT interval. Combination with agents that also prolong it may increase the risk of cardiac arrhythmias. In combination with serotonergic drugs, serotonin syndrome may occur. For this reason, concomitant administration of MAO inhibitors is also contraindicated. There have been reports of abnormal bleeding with SSRIs. Therefore, interactions with NSAIDs and other drugs that affect blood clotting are possible.
Adverse effects
Common adverse effects associated with therapy with SSRIs include: