I saw a client recently that contact me after trying many different medications over the past 20 years for trichotillomania, depression and anxiety, including several selective serotonin reuptake inhibitors (SSRIs) – like citalopram (Celexa), fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft) and escitalopram (Lexapro) – as well as bupropion (Wellbutrin), which is a selective norepinephrine-dopamine reuptake inhibitor. She was on some of these medications for years, but found that they “quit working” and she was either given another medication or an additional medication. Eventually, she found that none of them worked for her and that she was feeling worse than ever.
Reuptake inhibitors make the problem worse
I explained to her that reuptake inhibitors simply shuffle around neurotransmitters in the brain, giving the illusion of better health. You may feel better for a time, but at a price. Since the reuptake inhibitors don’t actually provide any raw materials, but artificially increase certain neurotransmitters in the brain, they actually cause a decrease in or further imbalance between neurotransmitters with time.
This occurs because the reuptake inhibitors work by preventing the reabsorption (the “reuptake”) of neurotransmitter into the pre-synaptic vesicle, thereby raising the synaptic levels of neurotransmitter. This provides the benefit of the drug. However, neurotransmitters in the synapse are not protected for degradation enzymes (like monoamine oxidase and COMT enzymes), which destroy them. As there are no additional raw materials coming in, over time, this causes a depletion of neurotransmitters.
Eventually, there aren’t enough neurotransmitters left for the reuptake inhibitors to shuffle around, and the drug “stops working”. Once more, the person is in a more depleted state at this point, as the use of the reuptake inhibitor has caused further neurotransmitter imbalance.
Raising neurotransmitter levels
Neurotransmitters themselves do not cross the blood-brain barrier. When neurotransmitters in the brain become depleted (by reuptake inhibitors or other causes) the only way to restore proper function is to increase neurotransmitter levels by taking the appropriate amino acid precursors for the necessary neurotransmitters.
Serotonin and dopamine are synthesized from the amino acid precursors 5-hydroxytryptophan (5-HTP) and L-3, 4-dihydroxyphenylalanine (L-dopa), respectively. L-dopa is synthesized from L-tyrosine. These precursors do cross the blood-brain barrier and can be freely made into their respective neurotransmitters. When the levels are high enough and in the proper balance, a resolution of symptoms is achieved.
If you’d like more information and references about how reuptake inhibitors decrease neurotransmitter levels, here are a couple places to get started: