Selective Serotonin Reuptake Inhibitors (SSRIs)

Table of Contents

What are SSRIs?

  • Selective Serotonin Reuptake Inhibitors (SSRIs) are a class of medications used to help individuals with depression, anxiety, obsessive compulsive disorder, post traumatic stress disorder, and many other psychiatric disorders.
  • These medications primarily work to enhance serotonin in the brain.
  • Serotonin is a chemical in our brain involved in many important functions including mood regulation, circadian rhythms (sleep), memory, and more.
  • There are very few studies, if any, comparing each medication with the others but we generally consider all SSRIs to be equivalent in terms of their efficacy for depression and anxiety
    • My clinical experience has been that not ALL are equal
  • Despite all medications having similar efficacy, they primarily differ in terms of side effects

What are common side effects of these medications?

  • Most Common Side Effects:
    • Nausea
    • Indigestion
    • Headache
    • Tremulousness
    • Sexual side effects: Anorgasmia, Delayed Ejaculation, Decreased libido
      • Paroxetine has high rate of sexual side effects compared to others
      • Sertraline has lower rate of sexual side effects compared to others
  • Bleeding Risk: All SSRIs carry a SMALL RISK for bleeding (remember that serotonin receptors are found on platelets)
  • Serotonin Syndrome: All SSRIs have the potential to cause serotonin syndrome but this is RARE and only occurs when taken in overdose or with other serotonin medications

How long does it take for these medications to work?

  • All SSRIs typically take 2-6 weeks (sometimes longer) before therapeutic effects are appreciated

Will I become dependent or addicted to these medications?

  • Addiction and dependence are different things
  • Addiction represents the behavioral changes in someone who begins altering their life to obtain or use something despite the negative consequences that occur when doing so (marital discord, health consequences, job loss, etc).
  • Dependence represents the physiological changes that occur after taking a medication or drug for a long time such that when the medication/drug is stopped there are withdrawal symptoms
    • If you stop taking a blood pressure medication after taking it for years, your blood pressure will likely “rebound” or increase. Therefore, you are considered dependent on your medication.
    • All SSRIs, with the exception of fluoxetine (Prozac), may cause a mild discontinuation (withdrawal) syndrome if stopped abruptly. However, if tapered appropriately, you are unlikely to experience a discontinuation syndrome

How long do I have to be on these medications?

  • It depends on the severity of your symptoms prior to starting the medication and whether you’ve experienced previous episodes of depression
  • However, the general recommendation is to take the medication for at least 9-12 months before beginning to taper off the medication.

Risk of Mania/Hypomania

  • All antidepressants carry a small risk of inducing a manic or hypomanic episode in patients with a preexisting diagnosis of bipolar disorder 
  • All antidepressants carry a small risk of causing “rapid cycling” (>4 mood episodes in a year) in patients with a preexisting diagnosis of bipolar disorder
  •  

It may get a little worse before it gets better

  • It isn’t uncommon to experience initial side effects such as a small increase in anxiety, tremulousness, nausea, and indigestion for 3-4 days BUT THESE ALMOST ALWAYS GO AWAY with continued use of the medication
  • The therapeutic effects of these medications are thought to result from the brain slowly adapting to the presence of the medication. This can take 2-6 weeks.

Final Points

  • Some patients complain of an “inability to feel” or a “flatness” feeling with inability to laugh, cry, or feel joy while taking SSRIs.
    • This usually resolves with reducing the dose or discontinuing the medication
  • In general (but not always), higher doses of SSRIs and SNRIs are needed to target anxiety disorder symptoms (OCD, PTSD, Generalized Anxiety) compared to doses needed for depression
  • Women tend to have more favorable responses to SSRIs than men
  • When using SSRIs in individuals with anxiety, we generally initiate the medication at a dose lower than the recommended starting dose and increase more slowly to prevent initial side effects

Overview of Each Medication:

  • Fluoxetine (Prozac)
  • Sertraline (Zoloft)
  • Paroxetine (Paxil)
  • Fluvoxamine (Luvox)
  • Citalopram (Celexa)
  • Escitalopram (Lexapro)

Half-Life: Fluoxetine 1-6 days; Norfluoxetine (Metabolite) 14-16 days
Starting Dose: 10mg-20mg PO once daily
Target Dosing Range: 20mg-60mg PO daily
BEST Time to dose: Morning
How to Dose:
>>Increase dose by 20mg every 4-6 weeks as tolerated until response.
>>If positive response, continue at that dose for at least 4-6 weeks
>>Use the minimum effective dose
>>Max dose 80mg/day
Pregnancy: Safe
breastfeeding: SAFE
FDA Indications:
1) Major depressive disorder (age 8 and older)
2) Obsessive-compulsive disorder (age 7 and older)
3) Panic disorder
4) Bulimia
5) Binge eating disorder
6) Premenstrual dysphoric disorder
7) Bipolar depression (as an adjunct with olanzapine also known as Symbyax)
8) Treatment-resistant depression when used in combination with olanzapine

 

ADDITIONAL INFORMATION:

  • Fluoxetine can be activating for many individuals and therefore is a good option for those with fatigue and low motivation but it might not be the best option for those with severe anxiety 
  • Fluoxetine (Prozac) and its metabolites have a very long half life (1-2 weeks) and therefore Fluoxetine (Prozac) rarely causes discontinuation (withdrawal) symptoms
  • In fact, fluoxetine (Prozac) is often used to treat discontinuation symptoms from abruptly stopping other SSRIs
  • Fluoxetine (Prozac) inhibits the metabolism of other medications and therefore interactions can occur.
  • Taking fluoxetine (Prozac) may cause other medications to become less effective (such as Tamoxifen and codeine)

HALF-LIFE: Sertraline 25hours; N-desmethylsertraline (metabolite) 2-3 days
STARTING DOSE: 25mg-50mg PO once daily
TARGET DOSING RANGE: 50mg-200mg
BEST TIME TO DOSE: Morning
HOW TO DOSE:
>> Initial 25mg PO daily
>> Increase by 25mg every 4-6 weeks as needed to max dose 200mg/day
>> Max dose 200mg daily (some may require up to 300mg/day)
PREGNANCY: SAFE
BREASTFEEDING: SAFE (minimal secretion in breast milk)
FDA INDICATIONS:
1) Major depressive disorder (age 8 and older)
2) Panic Disorder
3) Obsessive Compulsive Disorder
4) Social Anxiety Disorder
5) Post Traumatic Stress Disorder
6) Premenstrual dysphoric disorder

 

ADDITIONAL INFORMATION:

  • Sertraline (Zoloft) is very safe to take during pregnancy and while breastfeeding
  • Sertraline (Zoloft) is less likely to cause initial side effects

HALF-LIFE: <20 hours (no active metabolites)
STARTING DOSE: 10mg-20mg PO once daily
TARGET DOSING RANGE: 20mg-50mg PO daily
BEST TIME TO DOSE: Evening (at bedtime)
HOW TO DOSE:
>> Initial 10mg-20mg PO once daily
>> Increase dose by 10mg-20mg every 4-6 weeks
>> Max dose 50mg daily
PREGNANCY: AVOID IN PREGNANCY (if possible)
BREASTFEEDING: SAFE
FDA INDICATIONS:
1) Major depressive disorder
2) Panic Disorder
3) Obsessive Compulsive Disorder
4) Social Anxiety Disorder
5) Post Traumatic Stress Disorder
6) Generalized Anxiety Disorder
7) Premenstrual Dysphoric Disorder

 

ADDITIONAL INFORMATION:

  • Paroxetine (Paxil) is more likely than other SSRIs to cause sedation, weight gain, and dry mouth 
  • Paroxetine is a good choice for individuals with anxious type depression, especially when insomnia is prominent
  • Nitric Oxide Synthetase (NOS) inhibition is probably why paroxetine (Paxil) has greater propensity for sexual side effects in men
  • Paroxetine (Paxil) has no active metabolites and a relatively short half life which means it is likely to cause discontinuation syndrome if stopped too quickly
  • Paroxetine (Paxil), like Fluoxetine (Prozac),  interferes with the metabolism of certain medications and therefore may have clinically significant drug-drug interactions

HALF-LIFE: 15 hours 
STARTING DOSE: 50mg-100mg PO daily
TARGET DOSING RANGE: 100mg-200mg daily
BEST TIME TO DOSE: Any
HOW TO DOSE:
>> Initial 50mg-100mg PO once daily
>> Doses over 100mg/day of immediate release require BID dosing
>> Increase dose by 50mg/day every 1-2 weeks as tolerated
>> Max dose 200mg/day (some patient require doses up to 300mg/day)
PREGNANCY: AVOID, if possible (not enough data)
BREASTFEEDING: AVOID, if possible (not enough data)
FDA INDICATIONS:
1) Obsessive Compulsive Disorder
2) Social Anxiety Disorder

 

ADDITIONAL INFORMATION

  • Fluvoxamine (Luvox) was never approved for depression
  • Fluvoxamine (Luvox) is approved for Obsessive Compulsive Disorder and Social Anxiety Disorder

 

HALF-LIFE: 35 hours
STARTING DOSE: 10mg-20mg PO once daily
TARGET DOSING RANGE: 20mg-40mg PO daily
BEST TIME TO DOSE: Morning
HOW TO DOSE:
>> Initial 10mg-20mg PO once daily
>> Increase dose by 10mg every 4-6 weeks to max dose 40mg daily
>> Max dose 40mg/day (some may require up to 80mg/day)
PREGNANCY: SAFE
BREASTFEEDING: SAFE
FDA INDICATIONS:
1) Major depressive disorder

 

ADDITIONAL INFORMATION:

  • Minimal drug-drug interactions
  • Citalopram is well tolerated by most people, including elderly individuals 
  • There is a dose dependent risk of cardiac side effects with doses >40mg/day

Escitalopram

HALF-LIFE: 32 hours
STARTING DOSE: 5mg-10mg PO once daily
TARGET DOSING RANGE: 20mg-40mg PO daily
BEST TIME TO DOSE: Morning
HOW TO DOSE: 
>> Initial 5-10mg PO daily
>> Increase dose by 10mg every 4-6 weeks 
>> Max dose 40mg
PREGNANCY: SAFE
BREASTFEEDING: SAFE
FDA INDICATIONS:
1) Major depressive disorder 
2) Generalized Anxiety Disorder

 

ADDITIONAL INFORMATION:

  • Escitalopram (Lexapro) is the S-enantiomer of R,S-Citalopram (Celexa) 
  • Escitalopram is considered a “Pure SSRI” with minimal side effects
  • Almost no drug –drug interactions
  • Some evidence of QT prolongation at higher doses (>20mg) but this is controversial 

REFERENCES

  1. Cooper, J. R., Bloom, F. E., & Roth, R. H. (2003). The biochemical basis of neuropharmacology (8th ed.). New York, NY, US: Oxford University Press.
  2. Iversen, L. L., Iversen, S. D., Bloom, F. E., & Roth, R. H. (2009). Introduction to neuropsychopharmacology. Oxford: Oxford University Press.
  3. Puzantian, T., & Carlat, D. J. (2016). Medication fact book: for psychiatric practice. Newburyport, MA: Carlat Publishing, LLC.
  4. J. Ferrando, J. L. Levenson, & J. A. Owen (Eds.), Clinical manual of psychopharmacology in the medically ill(pp. 3-38). Arlington, VA, US: American Psychiatric Publishing, Inc.
  5. Schatzberg, A. F., & DeBattista, C. (2015). Manual of clinical psychopharmacology. Washington, DC: American Psychiatric Publishing.
  6. Schatzberg, A. F., & Nemeroff, C. B. (2017). The American Psychiatric Association Publishing textbook of psychopharmacology. Arlington, VA: American Psychiatric Association Publishing.
  7. Stahl, S. M. (2014). Stahl’s essential psychopharmacology: Prescriber’s guide (5th ed.). New York, NY, US: Cambridge University Press.
  8. Stahl, S. M. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (4th ed.). New York, NY, US: Cambridge University Press.
  9. Whalen, K., Finkel, R., & Panavelil, T. A. (2015). Lippincotts illustrated reviews: pharmacology. Philadelphia, PA: Wolters Kluwer.