Neurotransmitter-based diagnosis and treatment: A hypothesis (Part 1)

There are no well-recognized, well-established, reliable, or validated syndromes described in our work. Our goal is to suggest an alternative way of looking at psychiatric disorders by viewing syndromal presentation through the lens of specific neurotransmitters. The collection of symptoms associated with various neurotransmitters as presented in this hypothesis is not complete. We have assembled what is described in the literature as a suggestion for specific future research. We simplified these clinical presentations by omitting scenarios in which a specific neurotransmitter increases in one area but not another. For example, all the symptoms of dopamine excess we describe would not have to occur concurrently in the same patient, but they may develop in certain patients depending on which dopaminergic pathway is exhibiting excess activity. Such distinctions may be established only by exhaustive research not yet conducted.

Our proposal may seem radical, but it truly is not. For example, if we know that dopamine excess may cause seizures, psychosis, and blood pressure elevation, why not consider dopamine excess as an underlying cause in a patient with depression who exhibits these symptoms simultaneously? And why not call it “dopamine excess syndrome”? We already have “serotonin syndrome” for a patient experiencing a serotonin storm. However, using the same logic, it should be called “serotonin excess syndrome.” And if we know of “serotonin excess syndrome,” why not consider “serotonin deficiency syndrome”?

In Part 1 of this article, we discuss serotonin and dopamine. Table 1 outlines medical and psychiatric symptoms that likely reflect serotonin excess^2-18 and deficiency,^14,19-29 and Table 2 lists symptoms that likely reflect dopamine excess^14,30-41 and deficiency.^{4,14,20,38,40-43} In Part 2 we will touch on endorphins and norepinephrine, and in Part 3 we will conclude by looking at GABA and glutamate.

Serotonin excess (Table 1^2-18)

On a recent office visit, Ms. H reports that most of the time she does not feel much of anything, but she still experiences panic attacks^8,9,13,15 and is easily agitated.^6,8 Her mother died recently, and Ms. H is concerned that she did not grieve.^15-18 She failed her last semester in college and was indifferent to her failure.¹⁸ She sleeps poorly,⁸ is failing her creative classes, and wonders why she has lost her artistic inclination.^16-18 Ms. H has difficulty with amotivation, planning, social interactions, and speech.^16,17 All of those symptoms worsened after she was prescribed fluoxetine approximately 1 year ago for her “blues.” Ms. H is obese and continues to gain weight,² though she frequently has diarrhea,^3,4,7,8 loud peristalsis, and abdominal cramps.^4,7,8 She sweats easily^6-8 and her heart frequently races.^8,9 Additionally, Ms. H’s primary care physician told her that she has “borderline diabetes.”² She is prone to frequent bruising¹¹ and is easy to shake, even when she is experiencing minimal anxiety.^6-9 Ms. H had consulted with a neurologist because of unusual electrical “zapping” in her brain and muscle twitches.^5,8,9,13 She had experienced a seizure as a child, but this was possibly related to hypernatremia,² and she has not taken any anticonvulsant medication for several years.⁸ She exhibits hyperactive deep tendon reflexes and tremors^5,7,9 and blinks frequently.^6,9 She experiences hot flashes,^3,6-8,14 does not tolerate heat, and prefers cooler weather.^8,9 Her pains and aches,^12,14 to which she has been prone all of her life, have recently become much worse, and she was diagnosed with fibromyalgia in part because she frequently feels stiff all over.¹⁰ She complains of strange tingling and prickling sensations in her hands and feet, especially when anxious.^7,9,10 Her headaches also worsened and may be precipitated by bright light, as her pupils are usually dilated.^5,7,9 Her hypertension is fairly controlled with medication.^6,8-10 Ms. H says she experienced a psychotic episode when she was in her mid-teens,^6,8 but reassures you that “she is not that bad now,” although she remains hypervigilant.¹³ Also while in her teens, Ms. H was treated with paroxetine and experienced restlessness, agitation, delirium, tachycardia, fluctuating blood pressure, diaphoresis, diarrhea, and neuromuscular excitation, which prompted discontinuation of the antidepressant.^5-7,9,10

Impression. Ms. H exhibits symptoms associated with serotonin hyperactivity. Discontinuing and avoiding selective serotonin reuptake inhibitors (SSRIs) would be prudent; prescribing an anticonvulsant would be reasonable. Using a GABAergic medication to suppress serotonin (eg, baclofen) is likely to help. Avoiding dopaminergic medications is a must. Antidepressive antipsychotics would be logical to use. The use of serotonin-suppressing medications may be considered. One may argue for the use of beta-blockers in such a patient.

Continue to: Serotonin deficiency