Medications
Antidepressants
When we speak of antidepressants - we refer to medications that are used to treat clinical depression. The common and widely used first line antidepressants are called SSRIs (Selective Serotonin Reuptake Inhibitors). This name is derived from their action in the brain. They simplify block (at microscopic receptor level) the reuptake of neurotransmitters Serotonin. Scientific information has shown that by doing so an individual will see relief in depression and anxiety.
There are 6 types of SSRIs (see below). Mostly, they work in a similar way by blocking the reuptake of serotonin. But they have some key differences - such as half life (time it takes for a drug to reach 50 % of its original amount) and the type of receptors it works on. There are different types of Serotonin receptors with different subtypes that are spread throughout the brain. I will leave this subject here, or it gets too medically and pharmacologically technical.
Since the SSRIs work in a similar way their tolerance, adverse and side effect profile is quite similar. Although, some differences among them exist.
As you can see the effects of these medication occur at receptor levels in the brain. It is common to see the adverse effects early on in the treatment and not much benefits. This can be quite discouraging for individuals as they like to see quick result. So a standard duration to see the maximum benefits from these medication range between 4-8 weeks.
First, I will write about the collective adverse effects that are shared by all of these SSRIs with some subtle differences. Later, I will comment on the adverse effects that are unique to each medication.
Most Common Side Effects:
Nausea, Diarrhea or loose stools, appetite change (transient decrease), sexual side effects (mostly reversible - ranging from decreased libido to delayed or failure to ejaculation), tremor, dyspepsia (indigestion). Mostly common adverse effects occur early in treatment or with dose increases. A lot of times, most of the adverse effects are transient and goes away.
Other adverse effects: Usually rare
Hypersensitivity reaction to medication itself, Serotonin Syndrome, increased risk of bleeding, activation of hypomania or mania, discontinuation syndrome, hyponatremia, seizure.
If you are taking NSAIDs, aspirin or anticoagulants and antiplatelet medications - inform your clinician. Generally, SSRIs slightly interfere with platelets and may slightly increase risk of bleeding. Case reports have been made about bruises, hematoma, nosebleeds and gastrointestinal bleeds.
Discontinuation Syndrome:
Abrupt stopping of medication will lead to discontinuation syndrome. Symptoms range from - Nausea, sweating, dysphoric mood, dizziness, irritability, sensory disturbance (‘brain zaps’ - electric shock sensations), tremor, anxiety, headache, confusion, sleep disturbance. Usually occur in 2-3 days of abrupt stopping of medication, but with some medication may happen sooner or later. Generally, with long half life medication the risk of discontinuation syndrome is less.
Label Warning: In 2004 FDA added Blackbox warning - In pediatric patients antidepressants may increase the risk of suicidal thoughts and behavior. This warning was issued after some reports showed marginal increase in suicidal ideation in patient taking different antidepressants.
In 2007, adolescents and young adults aged <24 were added to this warning. Over the years, additional data has countered and questioned the link. However, as of now the warning stays in place. Therefore, close monitoring is important.
Pregnancy
-Not contraindicated in pregnancy, must weight risk and benefits of taking vs. not taking medication. There are exceptions - some SSRI (antidepressants have shown increased risks) - for example Paroxetine.
-Some studies reports birth defects but overall studies are inconclusive
- SSRI or SNRI medications in late pregnancy may increase risk of neonatal complications that may require prolonged hospitalization, respiratory support, tube feeding, pulmonary hypertension and drug discontinuation syndrome. Reported findings may present with - respiratory distress, cyanosis (bluish discoloration of skin, usually due to poor oxygenation), apnea, seizures, temperature instability, feeding difficulties, vomiting, tremor, jitteriness, constant crying, muscle tone problems.
SSRIs (Selective Serotonin Reuptake Inhibitor)
Sertraline (Zoloft)
Approved in 1991
FDA Approved Indication(s):
- Major Depression Disorder
- Obsessive-compulsive Disorder (OCD)
- Panic Disorder
- Social anxiety disorder
- PTSD (Posttraumatic stress disorder)
- PMDD (Premenstrual dysphoric disorder)
Other common uses: Generalized Anxiety Disorder
- Pediatric Patients:
OCD (Obsessive-Compulsive Disorder) - age 6 onward
- Dose range 25mg to 200mg. Comes in liquid as well - in some cases better tolerated
Fluoxetine (Prozac)
Fluoxetine (Brand Name - Prozac)
Approved in 1999
FDA approved for -
1. Major Depression Disorder (MDD) - approved for both the acute and maintenance of
depressive episodes.
2. Obsessive Compulsive Disorder (OCD)
3. Eating Disorder - Bulimia Nervosa type
4. Panic Disorder
It is also prescribed in combination with other medication Olanzapine (Zyprexa) in 2 situations.
- Treatment resistant depression - which means an individual failed to improve with at least 2 other antidepressants. The combination is called Symbyax (Fluoxetine + Olanzapine).
- Depression episode associated with Bipolar Disorder I. So, it is unique in a way that it is used by itself in unipolar depression and in combination with Olanzapine for Bipolar disorder I depression.
Dose Range:
20-80 mg daily, mostly comes in capsules.
It also comes in a once weekly dose of 90 mg/week.
Long half life
Fluoxetine has a long elimination half life. As a result it has an active metabolite that lasts for days after stopping medication. The benefit is, if it stopped abruptly or quickly - an individual is unlikely to see discontinuation symptoms.
Another point is when a dose is changed it will take upto few weeks to correlate the dose change to reflect in the body.
Caution in Elderly:
May see lowering of sodium known as hyponatremia. Look out for - headaches, dizziness, weakness, unsteady, difficulty with concentration, and memory troubles.
Escitalopram (Lexapro)
Approved in 2002
FDA approved for-
1. Major Depression Disorder
2. Generalized Anxiety Disorder
Other off label uses -
1. Social Anxiety Disorder
2. Obsessive- compulsive disorder (OCD)
3. Panic Disorder
4. Premenstrual Dysphoric Disorder (PMDD)
-Dosing: Generally started at 10 mg daily and increased to maximum 20 mg daily.
In come cases increased to 30 mg and upto 40 mg daily (although rare to increase upto 40 mg dose)
-Comes in tablet form (5 mg 10 mg and 20 mg) and liquid solution
-Generally weight neutral and no sedation. However, some people can feel tiredness or experience extra yawning
Citalopram (Celexa)
Approved 1998
FDA Indications-
1. Major Depression Disorder
Other off label uses -
1. Social Anxiety Disorder
2. Post Traumatic Stress Disorder (PTSD)
3. Panic Disorder
4. Obsessive Compulsive Disorder (OCD)
5. Premenstrual Dysphoric Disorder (PMDD)
6. Generalized Anxiety Disorder (GA)
Dosing -
-Range is 10 mg - 40 mg daily
-Comes in tablets and mouth disintegrating form pills
-Mostly started at 20 mg daily and increased to 30 or 40 mg dose
-Caution advised for individual with cardiac electric (conduction) abnormalities - Choose alternative or monitor closely if dose at or >40 mg daily.
-May see good results with anxiety related agitation, restlessness, irritability. Especially in the elderly with dementia cases.
-Unlikely to cause weight gain. Mild sedation as it has some histamine (H1) receptor antagonist activity. Lookout for mild drowsiness, dry mouth and fatigue.
Fluvoxamine (Luvox)
Approved1994
FDA Indications-
1. Social Anxiety Disorder - also known as Social Phobia
2. Obsessive-Compulsive Disorder (OCD)
Other off label uses -
1. Panic Disorder
2. Major Depression Disorder (MDD)
3. Generalized Anxiety Disorder GAD)
4 Posttraumatic Stress Disorder (PTSD)
Dosing -
It comes in two forms regular standard form and CR (controlled release form). CR is like saying extended release. In some cases CR is better tolerated. Another difference is CR remains once daily dose even at maximum recommended strength.
Range of dose is 25 mg to 300 mg for regular and controlled release is 100mg to 300 mg daily.
Works with serotonin receptor and in addition has activity as Sigma 1 receptors. The antagonist action at Sigma 1 may cause sedation, tiredness. In cases where anxiety cause insomnia and overactivation, it may provide good relief. If sedation is noted, best to take at night.
Usually no weight gain.
Paroxetine (Paxil)
Paroxetine - Approved 1992
Paroxetine CR (controlled release) approved 1999
Brand Names -
Pexeva 2003
Briselle 2013 - Indication for Vasomotor Symptoms (VMS) associated with menopause. It is Paroxetine but at lower dose of 7.5mg at bedtime.
FDA Indications:
1. Obsessive-Compulsive Disorder (OCD)
2. Major Depression Disorder (MDD)
3. Panic Disorder
4. Social Anxiety Disorder
5. PTSD
6. GAD
7. PMDD
Dosing:
Paroxetine: 10-50mg daily
Paroxetine CR: 12.5mg to 62.5mg daily
Oral Solution (Liquid)
-Sedation and weight gain (mostly form appetite boost) may be seen. In addition may note constipation, dry mouth
-Good in anxious, agitation depression cases
-Avoid in Pregnancy