some common and not-so-common, approved and unapproved treatments SSRIs and SNRIs are used for


Antidepressant Topic Index
SSRI & SNRI Overview and Topic Index | Why SSRIs & SNRIs are so popular, but are they right for you?

1.  FDA-Approved Indications

At least some SSRIs and SNRIs are approved to treat these conditions. Anything Celexa is prescribed for in the US, except depression, is an off-label (unapproved by the FDA) application. On the other hand, Prozac, Paxil (but not Paxil CR) and Cymbalta are approved to treat a shitload of stuff, some of which few other SSRIs or SNRIs are thrown at.

1.1  Depression. Duh.

In the US almost all serotonin-selective reuptake inhibitors (SSRIs) are approved to treat Major Depressive Disorder (MDD). Luvox (fluvoxamine) is the oddball, as it is only approved to treat OCD. Stress major, as there’s always one study after another showing how antidepressants only work for those of us with severe depression. If you’re functional every day of the week and you have a pretty good idea as to what is causing you to be depressed (other than your brain is screwed up and/or there’s a family history of severe depression), you should try therapy and lifestyle changes first. They’ll probably do you a hell of a lot more good.

1.2  Anxiety

Almost all SSRIs are approved to treat one or more conditions in the alphabet soup of the anxiety spectrum (GAD, OCD, SAnD, PD, PTSD). Celexa (citalopram) is the only SSRI approved in the US to treat depression and nothing else. It’s used off-label to treat anxiety disorders, and works rather well. Effexor and Cymbalta are approved to treat Generalized Anxiety Disorder (GAD). Effexor is also approved to treat Social Anxiety Disorder (SAnD) and Panic Disorder (PD). As of this writing Pristiq is like Celexa and is an MDD-only med. Given that Pristiq is essentially a more potent form of Effexor, it’s used off-label for which everything Effexor is approved and commonly used off-label.

1.3  Neuropathic Pain and Other Owies

As norepinephrine (NE) has more of an effect on pain than serotonin (5-HT), treating chronic pain is the realm of SNRIs. CymbaltaApprovedAndOffLabelUses is approved to treat Diabetic Peripheral Neuropathic Pain (DPN), Chronic Musculoskeletal Pain (CMP), and Fibromyalgia. Savella is approved in the US to treat only Fibro. Effexor has been used off-label to treat assorted pain conditions, including Phantom Limb Syndrome, but with Cymbalta and Savella now on the market it has been relegated to a third-line treatment, behind TCAs.

SSRIs are used off-label to treat chronic pain, but like Effexor, they’re a tertiary treatment option, behind TCAs with their greater effect1 on NE.


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2.  Totally Off-label Applications

Aside from using a med for something for which it isn’t approved but another SSRI or SNRI is, here are some things for which SSRIs and SNRIs are commonly prescribed and for which none is approved:

2.1  Bipolar Depression

  • It’s an off-label use anytime someone with Bipolar Disorder is prescribed any straight-up antidepressant.
  • The only med I have classified as an antidepressant approved to treat bipolar depression is Symbyax, and it’s a pre-mixed cocktail of Prozac and Zyprexa in one pill.
  • Other meds approved to treat bipolar depression are antipsychotics, such as Latuda and Seroquel.

2.2  Irritable Bowel Syndrome (IBS)

If the approved meds for this shitty condition didn’t do it for you:

  • PaxilApprovedAndOffLabelUses is especially popular.
  • Effexor is a strong number 2.
  • Since NE has a much greater constipating effect than 5-HT, you’d think SNRIs with a greater effect on NE would be used more often for the forms of IBS where you have the runs way more often.
    • So why Paxil and Effexor? Because your gut has vastly more 5-HT receptors than NE receptors, that’s (probably) why.
    • Paxil (and maybe Viibryd) are for people whose guts are basically leaking 5-HT all over the place, and they need to bind it up nice and tight.
    • Effexor (and maybe Pristiq) are for people whose guts’ grasp on 5-HT and NE need just a little tweaking.
    • Can you tell the difference before you try one or the other? Maybe. If there is a way I don’t know what it is. Sorry

2.3  Migraines and Other Headaches

  • TCAs are used off-label more often to treat headaches that aren’t responsive to the standard treatments, but all of the SSRIs & SNRIs get plenty of use as well.
  • This is probably because there are some forms of migraines that need daily serotonergic action to prevent them.
    • Using an abortive like a triptan every day is both prohibitively expensive and probably a bad idea for some other reason.
    • But the number of people who have them wasn’t enough to justify a drug company going through the expense of getting one of their meds approved for that use before it became available as a generic.
  • As far as the NE action provided by TCAs and SNRIs is concerned, your guess is as good as mine if that works to prevent the headaches, alleviate the pain, or a little of both.


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2.4  Premature Ejaculation

Gosh, I wonder why? Lexapro, Paxil, and Prozac are main meds used for this.

2.5  As Anti-Epileptic Drugs (AEDs)

What? Aren’t seizures a side effect of antidepressants? Yes, but mainly for Wellbutrin, or if you’re taking way too much, or if you were unlucky in side effect lotto. SSRIs can actually help prevent seizures, although you certainly wouldn’t want to take one as your only AED. SSRIs may have a very specific, a potentially life-saving property when it comes to epilepsy:

Ictal respiratory dysfunction occurs in patients with epilepsy and may contribute to sudden unexplained death in epilepsy (SUDEP). Fluoxetine reverses respiratory arrest in a mouse model of epilepsy, suggesting that selective serotonin reuptake inhibitors (SSRIs) may reduce ictal respiratory dysfunction. Video–electroencephalography (EEG) and pulse oximetry data from 496 seizures in 73 consecutive patients with partial epilepsy was reviewed, including 87 seizures in 16 patients taking SSRIs (SSRI+) and 409 seizures in 57 patients not taking SSRIs (SSRI)). The proportion of ictal-related oxygen desaturation <85% with partial seizures without secondary convulsions in SSRI+ patients was reduced relative to SSRI) patients (p = 0.011). There was no statistically significant difference in ictal oxygen desaturation for secondarily generalized convulsions. SSRIs are associated with reduced likelihood of ictal oxygen desaturation in patients with partial seizures. -- Serotonin reuptake inhibitors are associated with reduced severity of ictal hypoxemia in medically refractory partial epilepsy

In English: SSRIs can save your life by keeping you breathing when a seizure would otherwise cause you to suffocate because your brain hates you.2


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SSRI & SNRI Overview and Topic Index | Why SSRIs & SNRIs are so popular, but are they right for you?
Antidepressant Topic Index

1 Most TCAs have a greater effect on NE than 5-HT. There are a few, namely clomipramine, imipramine and amitriptyline, that have more of an effect on 5-HT than NE. The raw, freebase form of those drugs also have a greater effect on 5-HT than freebase fluoxetine, but that's just one aspect of potency. And potency has absolutely nothing to do with efficacy.

2 I have had up close and personal experience with this. Giving someone CPR in the midst of a flurry of seizures is just too much fun. Coming out of a seizure gasping for air is not to be missed either.
Since I have secondarily generalized seizures I'm not missing out on anything by not getting along with SSRIs.


Serotonin-Selective Reuptake Inhibitor (SSRI) and Serotonin & Norepinephrine Reuptake Inhibitor (SNRI) Uses by Jerod Poore is copyright © 2011 Jerod Poore
Date created: 1 July 2011 Last edited by: JerodPoore on: 2014–11–13





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1 While there are plenty of books to help you with hypochondria, for some reason there’s not much in the way of websites. Then again, staying off of the Internet is a large part of curing/managing the disorder.

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