Global Journal of Medical Research, A: Neurology & Nervous System, Volume 23 Issue 3

psychiatric symptoms have relatively high levels of neuronal excitability. This follows from the fact relatively minor stressors, which would be sufficient to precipitate psychiatric symptoms in persons with higher levels of neuronal excitability, are experienced much more often than the unusually high stressors that would be necessary to precipitate psychiatric symptoms in persons with lower levels of neuronal excitability [70]. Persons with higher levels of neuronal excitability would be more sensitive to stress both because their hyperexcitable neurons would abnormally amplify stress and because, over time, their hyperexcitable neurons would accelerate stress-induced kindling [19, 22]. Persons with higher levels of neuronal excitability would also be more likely to experience symptom-cycling because highly excitable neurons would have a greater propensity to facilitate aberrant circuit induction [23]. Treatment with antidepressants would further increase this risk because antidepressants (including SSRIs) have stimulatory effects on the brain [71, 72]. Hypothetically, this is what places such patients, who could be categorized as “bipolar spectrum,” at elevated risk for bipolar switching when treated with antidepressants. The more appropriate drugs for such patients would be anticonvulsants. Yet, because the symptom-cycling in such patients is often subclinical [42-44], and because neuronal hyperexcitability also tends to cause symptoms of ADHD [22], the vast majority of such patients are treated with antidepressants and psychostimulants. What creates even more confusion is that these drugs do tend to reduce symptoms, at least until the kindling that they fuel increases the overall level of excitation in the brain enough to offset their therapeutic effects [72, 73]. Until now, the failure to recognize this and the continued treatment of symptoms rather than neuropathology in psychiatric patients has resulted in the over-prescribing of antidepressants, psychostimulants, and other psychotropic drugs in lieu of anticonvulsants [28]. That is not to say that antidepressants are never helpful but only to say that they are more appropriate for the minority of patients who do not have hyperexcitable neurons. Such patients, who could be categorized as “true” unipolar depressives because of their relative resistance to symptom-cycling would, for the same reason, be unlikely to cycle even when treated with stimulating antidepressants. This is the MCNH explanation for why treatment with antidepressants has generally been found to be safer in patients with unipolar depression [74] than bipolar spectrum disorder [32, 75, 76]. However, considering the rarity of true unipolar depression in comparison to the high frequency with which antidepressants are prescribed [22, 77], the MCNH hypothesis also points to the weakness of symptoms alone as a guide to psychiatric pharmacotherapy. Clearly, the idea of treating nearly all of the common psychiatric disorders by reducing the excitability of the neurological system would simplify drug selection because it would highlight a biological target for which the treatment is evident. Thus, rather than chasing after specific symptoms with different classes of medication, such as anxiety symptoms with benzodiazepines, depressive symptoms with antidepressants, and psychotic symptoms with antipsychotics, a single non-benzodiazepine anticonvulsant or combination of anticonvulsants could be used to reduce all of these symptoms simultaneously. Note that in addition to simplifying drug selection and reducing medication load, this approach, which could be called “focused neuroregulation [78],” would circumvent the problem of ambiguous and overlapping diagnoses. Additionally, by reducing the total number of medications prescribed and replacing many brand-name drugs with generic ones, focused neuroregulation has the potential to reduce the side effect burden, medication costs, and conflicting effects that combining drugs from different classes can create. It also has the potential to simplify drug titration because anticonvulsants, which, based on their putative mechanism of action, could more aptly be called “neuroregulators” [79], exert their therapeutic effects in minutes rather than weeks. That means a patient could be started on a neuroregulator at an extremely low dosage and then titrated upward every one-to-two days rather than one-to-two weeks, as would be necessary with an antidepressant. It also means that any drug that was ineffective could be replaced much faster than when a drug takes several weeks to take effect. Moreover, because neuroregulators work to normalize brain function rather than modulate the activity of specific neuronal circuits, they can be combined with one another with relatively little risk of destabilizing mood, hence the term “mood stabilizer” [80-84]. V. M edication D osing The overprescribing of psychotropic drugs is not the only problem that begs to be addressed in modern clinical practice. The other is the dosing of psychotropic drugs. There are numerous factors that contribute to determining the optimal dosage of a medication for an individual patient. These include absorption and distribution, mechanism of action, receptor affinity, and metabolism and excretion. Although absorption and distribution are commonly assumed to be the most important of these, the actual contribution that each factor makes is highly specific to the individual. That underscores the importance of tailoring to the patient the quantity of drug prescribed. 28 Year 2023 Global Journal of Medical Research Volume XXIII Issue III Version I ( D ) A © 2023 Global Journals A Precision Medicine Approach to the Treatment of Psychiatric Disorders