Introduction

Antidepressant drugs are widely examined in pharmacy licensure exams. You can expect to see many NAPLEX questions on this topic. Today, we talk more about SSRIs, or selective serotonin reuptake inhibitors; the facts you need to know.

SSRIs have been around for quite some time. They were developed throughout the 1980s and, in 1987, the first SSRI – fluoxetine (Prozac) was released into the market. Since then, many more SSRIs have been introduced.

These include:

• Citalopram
• Escitalopram
• Sertraline
• Paroxetine
• Fluvoxamine

Below, we talk about what indications SSRIs are used to treat, how they work, what side effects and drug interactions they’re linked to, as well as what aspects of clinical pharmacy you are expected to know.

Let’s get started.

Indications

SSRIs are used in the treatment of the following conditions:

• Moderate-to-severe depression: SSRIs are a first-line treatment option. They are generally avoided in mild depression unless other treatment approaches fail.
• Panic disorder
• Obsessive compulsive disorder (OCD)

Of course, indications are not limited to these.

For example, sertraline has been used to treat premenstrual dysphoric disorder (PDD); a form of premenstrual syndrome that affects up to 8 percent of menstruating women.

Other conditions that SSRIs have been used to treat include post-traumatic stress disorder (PTSD), social anxiety disorder (SAD) and, in some cases, eating disorders such as bulimia nervosa.

SSRIs may also be used for other purposes not listed in this guide.

Mechanism of action

SSRIs work as selective serotonin reuptake inhibitors.

More specifically, SSRIs work to preferentially block neuronal reuptake of serotonin, also known as 5-hydroxytryptamine (5-HT). By inhibiting serotonin reuptake, more serotonin remains within the synaptic cleft to engage in further neurotransmission. This mechanism appears to be responsible for the antidepressant and anti-obsessive effects of these medicines.

Unlike tricyclic antidepressants (TCAs), SSRIs do not impact noradrenaline reuptake. SSRIs are preferred over TCAs, not least because the latter class of drugs are associated with a greater adverse effect profile.

Side effects

Side effects with SSRIs include:

• Gastrointestinal upset
• Loss of appetite
• Weight disturbances (either weight loss or gain)
• Photosensitivity
• Hyponatremia
• Increased risk of bone fractures
• Sexual dysfunction
• Lower seizure threshold
• QT prolongation
• Increased risk of serotonin syndrome
• Increased risk of bleeding

Though SSRIs are used as antidepressants, they may increase risk of suicidal ideation, particularly among younger patients.

Sudden withdrawal of SSRIs is not recommended. It can lead to neurological and influenza-like effects.

Serotonin syndrome risk increases with serotonergic drugs. These include linezolid, MAO inhibitors, lithium, tramadol, meperidine, TCAs, SNRIs and triptans.

Clinical pharmacology

Here are some of the key factors of clinical pharmacology of SSRIs you need to know:

• SSRIs interact with anticoagulant drugs such as warfarin, as well as antiplatelet drugs, such as aspirin – the net effect being an increased risk of bleeding. SSRIs are known to cause platelet dysfunction. NSAIDs also increase bleeding risk.
• SSRIs should be avoided with monoamine oxidase inhibitors due to the substantial risk of developing serotonin syndrome. See above for more drugs that also increase this risk.
• SSRIs should never be abruptly withdrawn. This can lead to pronounced and disturbing effects. Treatment should be withdrawn slowly, over time and with clinical oversight.
• SSRIs should be started on a low dose and increased over time. A standard starting dose, for example, may be 20mg citalopram. Depending on patient response – both therapeutic and in terms of adverse effects – this dose will be adjusted accordingly.
• Patients must be counselled that therapeutic effects do not manifest overnight. It may take many weeks, perhaps 3-6 months, before substantial clinical benefit is seen. Patients should be warned not to discontinue treatment suddenly.
• QT prolongation risk increases with other drugs that also increase the same risk. This include fluoroquinolones, amiodarone, antipsychotics, macrolides and quinine.
• Increased risk of seizures when SSRIs are given to patients with epilepsy.
• Citalopram and escitalopram are associated with fewer adverse effects compared to other SSRIs.

SSRIs remain an important therapeutic choice for a wide variety of psychological disorders.

Their use, for some, remains controversial. The monoamine theory that underpins their use has been called into question. Many studies question the relative efficacy of these medicines, claiming that they are not much better than placebo.

Regardless of the ongoing debate, they remain an important clinical option and, given their side effect, drug interaction and clinical risks, remain an essential topic for students taking their pharmacy licensure exam.

For more pharmacy questions on SSRIs and other antidepressants, register with NAPLEX Study Guide today. We remain the leading online resource that helps students pass their pharmacy exam first time, every time.