Neurotransmitter-based diagnosis and treatment: A hypothesis (Part 2)

There is a need to connect mental and physical symptoms in the diagnosis and treatment of psychiatric disorders. Obviously, we are not yet equipped to clearly recognize which neurotransmitters cause which symptoms. The science of defining the underlying mechanisms is lagging behind the clinical needs. However, in this article, we present a few hypothetical clinical cases to emphasize a possible way of analyzing symptoms in order to identify underlying pathology and guide more effective treatment. Our descriptions do not reflect the entire set of symptoms caused by these neurotransmitters; we created them based on what is presently known (or suspected). Additional research is needed to confirm or disprove the hypotheses we present.

In Part 1 (Current Psychiatry, May 2022), we argued that for depression, anxiety, psychosis, and bipolar disorder, development and approval of medications is currently based on descriptive diagnoses, with disregard to the various underlying causes of those conditions. Similar to how the many types of pneumonia are treated differently based on the specific infective agent, we suggested there are various types of depression or chronic pain based on the underlying neuro­transmitter pathology. Such an approach may be extrapolated to anxiety, psychosis, or bipolar disorder, although those conditions are outside the scope of this article. In Part 1, we described serotonin- and dopamine-associated mental and physical symptoms that suggest distinctly different types of depression or chronic pain, and we suggested specific ways of treating those described conditions. Part 2 reflects on pathology that is possibly connected to endorphin and norepinephrine dysfunction. Table 1 outlines medical and psychiatric symptoms that likely reflect endorphin excess^1-16 and deficiency,^1,16-24 and Table 2 lists symptoms that likely reflect norepinephrine excess^16,25-30and deficiency.^16,26,31-39 It is worth noting that both the quantity of neurotransmitters as well as the quality of the transmission (as in receptors, cellular pumps, and distribution mechanisms) are important.

Endorphin excess (Table 1^1-16)

Ms. R is a frustrated chronic pain patient who bitterly complains that despite having seen more than 20 physicians, she does not have an answer to what causes her “all over” pain and headache.^4,5,11 She does not believe that all her laboratory test are normal, and insists that “something is missing.” She aches all over but says she can actually tolerate more pain than others and experiences only a little discomfort during an electromyogram or dental interventions. Though Ms. R is not very susceptible to acute pain,^4,5,9,16 pain all over without an identifiable cause is part of her life.^4,5,11 She says that listening to music and social interactions help decrease her pain.^4,5,10 Ms. R states that opioid medications do not help her pain, though she has a history of opioid overuse and opioid-induced hyperalgesia.^6,11,16

Ms. R tends to overdo pleasureful activities to achieve satisfaction.² She says exercise is particularly satisfying, to the point that she experiences euphoria and a loss of time.⁹ She is angry that her neurologist suggested she see a psychiatrist. Her depression bothers her more than her anxiety.^2,5,7

Ms. R clearly has a self-image problem, alternating between high and low self-esteem. She has a low appetite^1,12,14-16 and sleeps excessively.^2,4,7,9,10 Her mother privately tells you that Ms. R has a history of childhood sexual abuse and lagged in life due to a lack of motivation. Ms. R used to self-mutilate “to feel normal.”¹² Her primary care physician chronically addresses Ms. R’s poorly explained cholestasis and pruritus⁸ as well as dysregulation of blood pressure and heart rate, both of which tend to be low.^12,13,16

Impression. Ms. R shows multiple symptoms associated with endorphin excess. A trial of an opioid antagonist may be reasonable. Dopamine blockade helps with endorphin suppression and also may be used for this patient. Using a low starting dose and a slow titration of such medications would be beneficial due to frequent intolerance issues, especially nausea. Gamma aminobutyric acid-ergic medications modulate the opioid system and may be considered. A serotonin-norepinephrine reuptake inhibitor (SNRI) or mirtazapine may help patients such as Ms. R to control mood and pain through norepinephrine’s influence on endorphins.

Endorphin deficiency (Table 1^1,16-24)

Mr. J complains of low back pain, diffuse body pain, depression, and moodiness.^19,20,24 He is sluggish and plagued by psychomotor retardation.²⁴ All his life, a heightened perception of pain has caused him problems,^19,20 but has not stopped him from engaging in self-mutilation.²⁴ His “unexplained” pain and general body aches seem to be associated with objectively verifiable pain generators (such as bruises and surgical procedures) but this pain is in excess of what would generally be expected. Mr. J describes his low back pain as mild degenerative disc disease and is eager to explain that his wife’s spine is more diseased, yet she has no back pain.

Continue to: Mr. J responds to treatment...