Selective Serotonin Reuptake Inhibitors (SSRI)

Five misconceptions about antidepressants… and what science is ...

SSRI Antidepressants

The SSRIs first were prescribed in the United States in the late 1980s. They are now the most widely prescribed class of antidepressant medications. Today, over two-thirds of the prescriptions for SSRIs are written by non-mental health practitioners.

In 2010, antidepressant prescriptions were purchased by 9.9% (23.3 million) of the pre-adolescent and older U.S. population, for a total of 212.5 million prescriptions. During 2011–2014, 12.7% of people were 12 years of age. And older had taken antidepressant medication in the past month.

In the United States, one of the most widely prescribed drugs are antidepressants. And SSRIs/SNRIs account for roughly 85% of these prescriptions. At this time, the Food and Drug Administration (FDA) has approved the following SSRIs for the treatment of depression:

    • Prozac (fluoxetine)
    • Paxil (paroxetine)
    • Zoloft (sertraline)
    • Celexa (citalopram)
    •  Lexapro (escitalopram)

SSRI Side Effects

Side effects largely contribute to the 31% to 60% non-adherence rate with antidepressants.

SSRI Sexual Dysfunction

Sexual side effects are the most frequent antidepressant side effect reported by primary care patients.  In a study involving 2,163 adults who had undergone at least eight weeks of treatment with antidepressants, 79% showed some degree of sexual dysfunction. Dysfunction varies from decreased libido to inability to obtain orgasm, and erectile difficulty.

Managing Antidepressant Sexual Side Effects

In both men and women, antidepressant-induced sexual side effects largely result from increased serotonin (5-HT) neurotransmission via reuptake blockade of serotonin transporters. Antidepressants that primarily increase dopamine and norepinephrine neurotransmission produce markedly fewer sexual side effects.

This provides the rationale for treatment using bupropion and other agents that simultaneously increase norepinephrine and dopamine signaling. It also suggests the theoretical basis for developing novel antidepressants that increase 5-HT and dopamine signaling. These findings are clinically relevant for patients who develop sexual side effects. And also attain substantial clinical improvement or remission of depression with serotonergic agents.

Serotonergic antidepressants produce the highest rates of sexual side effects.

Other mechanisms

Other possible mechanisms for SSRI sexual side effects include decreased dopaminergic transmission, cholinergic and alpha-adrenergic blockade. And inhibition of nitric oxide synthase 1, and prolactin elevation.

The American Psychiatric Association recommends we need to ask men and women whether sexual side effects are occurring with these medications.

Sexual dysfunction is under-reported if it is not specifically examined by clinicians. Because patients will not report sexual side effects due to embarrassment or perhaps due to lack of recognition of those symptoms as medication-related.

The association between major depressive disorder and sexual dysfunction is bidirectional. Moreover, estimated prevalence rates of antidepressant-induced sexual side effects are very high for several antidepressants. But the estimation of true prevalence is complicated by the high prevalence of sexual dysfunction in all patients. With mood disorders and by the under-reporting of sexual side effects.

Baseline sexual functioning should be assessed with validated rating scales at the same time depression is evaluated.

“Your worst enemy cannot harm you as much as your own unguarded thoughts.”

SSRI Weight Gain

Weight gain occurs most often after prolonged treatment with SSRIs. Although weight loss is common during the first few weeks of treatment.

Studies have documented problems of unwanted weight gain with SSRIs. For many patients, weight gain is an intolerable side effect.  Meta-analyses have shown that although weight gain is a common side effect of antidepressants. The average weight gain per patient is small.  For those patients who experience significant weight gain. It is likely that multiple factors in addition to drug mechanisms are contributory. That also including genetic predisposition.

If significant weight gain occurs, it is typically gradual over the course of many months. And does not appear to depend on the dosage.

Moreover,  a 7% weight change translates to 11 pounds for a 150-pound person. Patients are willing to gain only an average of 5.37 pounds as a side effect of medication use in the treatment of a non-life-threatening psychiatric condition. Therefore, in this example (a 150-pound person). An approximate 5-pound weight difference exists between clinical significance (the area of practitioner’s concern). And the weight gain patients are willing to tolerate from SSRIs.  Discontinuation of antidepressants occurs 62% of the time during the acute phase of treatment. And 66% during the late phase of treatment due to side effects.

More importantly

More importantly, it must be acknowledged that there are no definitive studies that clearly demonstrate the use of SSRIs causes weight gain in a majority of participants. However, many of the current studies demonstrate weight gain in some subjects. Especially during long term treatment.  After the response to prevent relapse and provide maintenance treatment.

Weight gain caused by SSRIs can affect a patient’s physical health, appearance, self-confidence, self-esteem and feelings of self-worth. Positive body perception is an important part of self-image.


SSRI Sedation

Sedation is more common with medications that have histamine-blocking or alpha-receptor blocking. Although all SSRIs can cause sedation. The most sedating SSRIs are Luvox (fluvoxamine), Paroxetine (Paxil), and Citalopram (Celexa).

Increasing daytime exercise can also be beneficial. If the SSRI is very effective. It may be worth adding a stimulating medication such as Wellbutrin, Provigil, or Strattera.

If dosing adjustments and augmentation are not beneficial. A switch to a non-sedating antidepressant may be necessary.

“Mental pain is less dramatic than physical pain, but is more common and also more hard to bear. The frequent attempt to conceal mental pain increases its burden: It is easier to say ‘My tooth is aching’ than to say ‘My heart is broken.'”

C.S. Lewis

SSRI Activation

Activation from SSRIs can be in the form of anxiety, jitteriness, insomnia, or agitation/irritability. It usually subsides within the first few weeks of treatment. But it can be very distressing. Patients with antidepressant-induced activation should not reduce their medication. But may need a temporary dosage reduction or a more gradual increase of the dosage.

Of the SSRIs, Prozac (fluoxetine) is the most likely to cause activation. The latter is due to the effects Zoloft has on dopamine receptors. Although activation can be troublesome, it can be helpful for those with severe fatigue. Low motivation, or excessive sleepiness.

SSRI Gastrointestinal Side Effects

In the short term, the most common side effects of SSRIs are nausea, vomiting, and diarrhea.

Intestinal health; knowing your second brain is vital!

Management to decrease nausea include:

  • lowering the dose
  • dividing the dose
  • taking the dose with food
  • taking OTC medications (Pepto-Bismol)