Noradrenaline re-uptake inhibitors

Venlafaxine is a serotonin and noradrenaline re-uptake inhibitor indicated in depression and may be used in generalised anxiety disorder. Venlafaxine can cause diarrhoea and headache as side-effects. It does not cause blurred vision. 

The noradrenaline re-uptake inhibitor, reboxetine, does not cause weight gain during routine clinical use and indeed has been advocated as an adjunctive treatment in the management of olanzapine-induced weight gain. 

These data suggest that antidepressant-induced sexual dysfunction is more likely to be associated with agents that greatly potentiate 5HT neurotransmission. This notion is supported by the results of a 6-week doubleblind study of 24 men with premature ejaculation, in which paroxetine (20 mg/day) increased latency to ejaculation six-fold while mirtazapine (30 mg/day) had minimal effect (4). In a randomized, 8-week, double-blind, placebo-controlled study in 450 patients with major depression, fluoxetine (20 -0 mg/day) significantly impaired sexual function, while the noradrenaline re-uptake inhibitor reboxetine had no effect (5). 

Hyponatremia with SSRIs is well described (SEDA-27, 12) but has also been reported with other antidepressants, including the selective noradrenaline re-uptake inhibitor reboxetine. 

Duloxetine has recently been marketed as an antidepressant in Europe. It inhibits the re-uptake of serotonin and noradrenaline, with minimal effects on other neurotransmitter mechanisms. It is therefore classified as a serotonin and noradrenaline re-uptake inhibitor (SNRI) and is grouped with venlafaxine. The adverse effect profile of duloxetine appears to be similar to that of the SSRIs and venlafaxine. In placebo-controlled trials the most common adverse effects were nausea (37%), dry mouth (32%), dizziness (22%), somnolence (20%), insomnia (20%), and diarrhea (14%). Sexual dysfunction has also been reported. Current data suggest that, unlike venlafaxine, duloxetine does not increase the blood pressure, but further post-marketing surveillance studies will be needed to confirm this (1). 

Reboxetine is a selective noradrenaline re-uptake inhibitor with low affinity for a-adrenoceptors and muscarinic receptors. In controlled trials the following adverse events occurred significantly more often with reboxetine than with placebo dry mouth (27%), constipation (17%), increased sweating (14%), insomnia (14%), urinary... 

A 72-year-old woman taking venlafaxine 150 mg/day for depression was abruptly switched to the noradrenaline re-uptake inhibitor maprotiline 75 mg/day 1 day later she developed agitation, sweating, nausea, vomiting, tinnitus, and insomnia (27). These symptoms continued for another week, but disappeared on the second day of sertraline treatment 50 mg/day. 

Zinner NR. Duloxetine a serotonin-noradrenaline re-uptake inhibitor for the treatment of stress urinary incontinence. Expert Opin Investig Drugs 2003 ... 

One of the adverse effects of reboxetine is difficulty in passing urine (SEDA-21,13). Eight patients taking reboxetine (4-8 mg/day) had troublesome urinary hesitancy (3). They were successfully treated with tamsulosin (0.4 mg/day), and in two patients tamsulosin was withdrawn after 2 weeks without recurrence of the urinary symptoms. Reboxetine is a selective noradrenaline re-uptake inhibitor and may therefore produce urinary symptoms by activating ai-adrenoceptors in the bladder, which tamsulosin would be expected to reverse. However, tamsulosin is also effective for urinary symptoms caused by other mechanisms, for example benign prostatic hyperplasia. Whether its apparent effectiveness in reboxetine-induced dysuria represents specific pharmacological antagonism is therefore uncertain. 

The symptoms experienced by this patient were tjrpical of venlafaxine and SSRI withdrawal (although they could also be experienced after sudden withdrawal of tricyclic antidepressants). The fact that they were relieved by a serotonin but not a noradrenaline re-uptake inhibitor suggests that venlafaxine-induced withdrawal symptoms are mediated by serotonergic mechanisms. 

Tramake Tramal Zydol ) is a phenylcyclohexanol derivative, a (p) OPIOID RECEPTOR agonist with partial OPIOID ANALGESIC activity. It is also a monoamine (serotonin and noradrenaline) re-UPTAKE inhibitor, and this mechanism is thought independently to contribute a component to analgesic activity. 

Serotonin and Noradrenaline Re uptake Inhibitors (SNRIs) Side effects similar to SSRIs, especially GI (constipation, dry mouth, nausea), sedation/insomnia. Added risk of hypertension... 

---