SSRI/SNRI antidepressants

see also:

• antidepressants
• Serotonin physiology

• selective serotonin reuptake inhibitors are primarily used for Rx of depression and are the 1st line agents for drug Rx of anxiety disorders, panic attacks, hyperventilation including OCD.
• they are also used in Rx of premature ejaculation
• whilst being much safer than earlier antidepressants, particularly in overdose, there are increasing concerns that their efficacy may be more limited than previously assumed.
• A 2010 meta-analysis states that “The magnitude of benefit of antidepressant medication compared with placebo … may be minimal or nonexistent, on average, in patients with mild or moderate symptoms. For patients with very severe depression, the benefit of medications over placebo is substantial¹⁾
• Furthermore, a double blind randomised trial involving 326 UK patients with Alzheimer’s disease and depression, no clinical benefit was seen with the use of sertraline or mirtazapine for up to 39 weeks, compared with placebo.²⁾
• a related class of antidepressants are the serotonin-norepinephrine reuptake inhibitors (SNRI's) share many of the adverse effects of SSRI's.

• General side effects are mostly present during the first 1–4 weeks while the body adapts to the drug (with the exception of sexual side effects, which tend to occur later in treatment)
• anhedonia, decreased libido, delayed ejaculation and anorgasmia
• genital hypothesia (reduced sensitivity) - appears to be 10-fold higher in past users of SSRIs compared to anti-psychotics in youths ³⁾
• apathy
• bruxism
• tinnitus
• urinary retention
• insomnia
• weight loss
• increased risk of bone fractures
• anxiety / panic attacks / suicidal ideation
• Parkinsonism in the elderly
• autonomic dysfunction including postural hypotension
• akathisia
• syndrome of inappropriate ADH secretion (SIADH)
• serotonin syndrome- especially in overdose or when used with other medications including St John's Wort, tramadol, pethidine, etc.
• the abrupt discontinuation usually leads to withdrawal, or “discontinuation syndrome” consisting of anxiety and other symptoms.
• 2011 study suggests SSRI's taken in the year before prgnancy doubles risk of autism spectrum disorder and if taken in 1st trimester, quadruples the risk (J. Arch. General Psychiatry)

• citalopram (Celexa, Cipramil, Cipram, Dalsan, Recital, Emocal, Sepram, Seropram, Citox, Cital)
• dapoxetine (Priligy)
• escitalopram (Lexapro, Cipralex, Seroplex, Esertia)
• fluoxetine (Prozac, Fontex, Seromex, Seronil, Sarafem, Ladose, Motivest,Flutop, Fluctin (EUR), Fluox (NZ), Depress (UZB), Lovan (AUS))
• fluvoxamine (Luvox, Fevarin, Faverin, Dumyrox, Favoxil, Movox)
• indalpine (Upstene) (discontinued)
• paroxetine (Paxil, Seroxat, Sereupin, Aropax, Deroxat, Divarius, Rexetin, Xetanor, Paroxat, Loxamine, Deparoc)
• sertraline (Zoloft, Lustral, Serlain, Asentra)
• vilazodone (Viibyrd)
• zimelidine (Zelmid, Normud) (discontinued)

• The first and most commonly used SNRI.
• Introduced in 1994.
• The reuptake effects of venlafaxine are dose dependent. At low doses (<150 mg/day) it acts only on serotonergic transmission. At moderate doses (>150 mg/day) it acts on serotonergic and noradrenergic systems, whereas at high doses (>300 mg/day) it also affects dopaminergic neurotransmission.

• the active metabolite of venlafaxine
• introduced in Australia in 2009 as Pristiq
• usual dose 50mg daily
• higher doses seem to add adverse effects without added benefit

• duloxetine (Cymbalta, Yentreve)
• milnacipran (Dalcipran, Ixel, Savella)
• levomilnacipran (F2695)
• sibutramine (Meridia, Reductil)
• bicifadine (DOV-220,075)
• vortioxetine (Brintellix)
  • introduced 2015
  • “multimodal”: SSRI + has agonist or antagonist activity at various 5-HT receptors
  • 5mg doses may be adequate in elderly but need 10-20mg in younger adults although nausea and sexual dysfunction may be problematic at higher doses