NoFap pharmacist answers question about ED & SSRIs

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SSRI antidepressants


Pharmacist answer.

There are two theories regarding the delay in efficacy of SSRI's. These medications work by inhibiting the SERT transporter, which ordinarily flushes serotonin out of the synapse and back into the pre-synaptic neuron for recycling into vesicles for reuse.

The old school of thought suggested that achieving a steady level of serotonin in the synapse took a few weeks. But, we know because of animal studies that this is not true. Therapeutic serotonin levels are achieved within hours to days depending on which one of the SSRI's you are taking. Fluoxetine, for example, has a long elimination half-life. This means that a steady level of the drug in the patient's blood won't even be achieved for several days after starting the medication.

The newer school of thought states that the changes in mood are actually caused by "downstream" effects of a constant level of serotonin at the synapse. These effects begin with serotonin, but are thought to be mediated by protein transcription from DNA and RNA (or possibly micro-RNA). There are some G-protein linked receptors that are affected by serotonin as well which affect cellular levels of cyclic AMP.

If this "downstream" theory is true, the process of protein creation takes considerable time and would account for the delay. It is also interesting to note that the medication Buspar (buspirone), which binds the serotonin receptor directly (and does not rely no any sort of accumulation) also takes a few weeks to work. This further supports the protien-mediation theory.

In addition, it has been observed that the SERT (reuptake) transpoters (which often exist in higher-than-normal quantities in depressed individuals) actually begin to decrease in number with continued administration of an SSRI. This is thought to further increase synaptic levels of serotonin and augment the long-term effects of an SSRI (Zhao et al., 2009).

A couple studies have also shown that SSRIs cause generation of new neurons from progenitor cells in the dendrate nucleus of the hypocampus and subventricular zones, which by definition, must be DNA mediated. (Santarelli, et. al 2003, Manganas et al., 2007.) These additional neurons may have some placating effect on anxiety and depression.

There may be more to learn about the mechanism of effect of SSRI's. However, the side-effects on sexuality are well established.

SSRI's can cause ED, delayed ejaculation, in men, impaired arousal, dryness in women, and anorgasmia in men and women. Generally we classify the drug-effects on sexual dysfunction in men by the way they effect either the parasympathetic or sympathetic nervous systems, respectively. The PNS and SNS both facilitate different parts of the male sexual response. A good way to remember this is: P is for point, S is for shoot. Unfortunately, SSRIs affect both systems.

SSRIs are all similar in shape to anti-cholinergic drugs and all have some anticholinergic effects (dry eyes, mouth, urinary hesitancy, delayed ejaculation). They also cause a reflexive reduction in dopamine transmission, which impairs pleasure and arousal. There is also limited evidence that SSRIs inhibit erection directly by interfering with the production of Nitric Oxide, which is the main vasodilator that causes erection.

If I remember correctly, sexual side effects burden some 40% of female patients and up to 70% of male patients on SSRIs. Some folks can get relief with a drug like Viagra (including women). However, usually, if you are in the population that suffers sexual dysfunction, the most helpful thing is to try a different medication or lower your dose. All sexual side-effects are dose-dependent.

Alternative antidepressant/antianxiety meds to SSRI's which typically cause less sexual dysfunction are Wellbutrin (bupropion) and Remeron (mirtazapine). These two meds work in different ways and I would try BOTH before I gave up on medication altogether. As always, exercise and cognitive behavioral therapy (CBT) work well for depression and anxiety and they work even better in combination with medication.

In regard to your statement about response, keep in mind that the initial response rate (which is somewhere around 15-18%) jumps to 30% or so when you reevaluate in 4 weeks and either increase dose or switch meds if response was inadequate. Combined with CBT and exercise, medication can bring about remission in about 2/3 of all patients, given enough time for adjustments to therapy. In my field, 2/3 response is pretty damn good.

If you have further questions about these drugs or the topic in general, don't hesitate to ask. Hope this helps.