Ultrarapid metabolizers break down doxepin much faster than extensive metabolizers; patients with this metabolizer type may have a greater chance of experiencing pharmacological failure. A study assessed the metabolism of a single 75 mg oral dose of doxepin in healthy volunteers with genetic polymorphisms in CYP2D6, CYP2C9, and CYP2C19 enzymes. In CYP2D6 extensive, intermediate, and poor metabolizers, the mean clearance rates of (E)-doxepin were 406, 247, and 127 L/hour, respectively (~3-fold difference between extensive and poor). In addition, the bioavailability of (E)-doxepin was about 2-fold lower in extensive relative to poor CYP2D6 metabolizers, indicating a significant role of CYP2D6 in the first-pass metabolism of (E)-doxepin. The clearance of (E)-doxepin in CYP2C9 slow metabolizers was also significantly reduced at 238 L/hour. CYP2C19 was involved in the metabolism of (Z)-doxepin, with clearance rates of 191 L/hour in CYP2C19 extensive metabolizers and 73 L/hour in poor metabolizers (~2.5-fold difference). Area-under-the-curve (0–48 hour) levels of nordoxepin were dependent on the genotype of CYP2D6 with median values of 1.28, 1.35, and 5.28 nM•L/hour in CYP2D6 extensive, intermediate, and poor metabolizers, respectively (~4-fold difference between extensive and poor). Taken together, doxepin metabolism appears to be highly stereoselective, and CYP2D6 genotype has a major influence on the pharmacokinetics of (E)-doxepin.
: 174 The related schizotypal personality disorder and schizophrenia are reported to have ties to creative thinking, and it is speculated that the internal fantasy aspect of SzPD may also be reflective of this thinking. Alternatively, there has been an especially large contribution of people with schizoid symptoms to science and theoretical areas of knowledge, including maths, physics, economics, etc. At the same time, people with SzPD are helpless at many practical activities because of their symptoms. Secret schizoids
Many schizoid individuals display an engaging, interactive personality, contradicting the observable characteristic emphasized by the DSM-5 and ICD-10 definitions of the schizoid personality. Guntrip (using ideas of Klein, Fairbairn and Winnicott) classifies these individuals as "secret schizoids", who behave with socially available, interested, engaged and involved interaction yet remain emotionally withdrawn and sequestered within the safety of the internal world. : 17  Klein distinguishes between a "classic" SzPD and a "secret" SzPD, which occur "just as often" as each other. Klein cautions one should not misidentify the schizoid person as a result of the patients defensive, compensatory interaction with the external world. He suggests one ask the person what their subjective experience is, to detect the presence of the schizoid refusal of emotional intimacy and preference for objective fact.Frequently, a schizoid individuals social functioning improves, sometimes dramatically, when the individual knows they are an anonymous participant in a real-time conversation or correspondence, e.g. in an online chatroom or message board. It is often the case the individuals online correspondent will report nothing amiss in the individuals engagement and affect.