Anxiety Answers

It’s well known that cortisol accelerates the aging process, and Dr. Peat has written extensively about the destructive effects of both prolactin and cortisol, where it’s ideal to keep prolactin under a lab value of 9.
Buspirone, an anxiolytic medication used to treat generalized anxiety disorder (GAD) increases cortisol and prolactin concentrations, so it has detrimental hormonal effects, similar to most SSRI’s.
“The cortisol response to ipsapirone (a 5-HT1A-partial agonist that produces a dose-dependent increase in plasma cortisol secretion in man) is blunted in major depression. Buspirone is another 5-HT1A agonistthat increases cortisol secretion in man. This study investigated cortisol and prolactin (PRL) responses to buspirone (30 mg orally) in 45 major depressed subjects and 28 normal controls. Buspirone administration yielded a significant increase in cortisol and PRL levels in both normal controls and depressed subjects. No differences in buspirone-induced hormone responses were found either between major depressives and normal controls or between melancholic and nonmelancholic depressives. There were no significant relationships between severity of depression and any of the hormonal responses to buspirone. PRL responses to buspirone were significantly higher in women than in men.”

Dr. Peat has wrote about the tendency of histamine (largely promoted by estrogen in the context of an inflammatory response) to promote nerve excitation and cause anxiety. Antihistamines can treat anxiety disorders, and they lack the negative effects of benzodiazepine drugs, such as mitochondrial fragmentation and predisposition to neurodegenerative diseases (including severe amnesia), as well as physical addiction and withdrawal symptoms including seizures.
Many drugs with antihistamine effects, including the tricyclic antidepressants (TCA’s) prolong the QT-interval (a process detrimental the heart’s ability to contract,) particularly amitriptyline and imipramine, but also the newer generation tetracyclic antidepressant mirtazapine, serotonin-norepinephrine reuptake inhibitors (SNRI’s), selective-serotonin reuptake inhibitors (SSRI’s) and so on.
Hydroxyzine mildly prolongs the QT-interval, but the drug doesn’t possess the long-term neurodegenerative potential of the benzodiazepine drugs. The antihistamine cyproheptadine does not prolong the QT-interval, but it can cause severe weight gain if taken in therapeutic dosages to treat anxiety. Hydroxyzine has a lower propensity for weight gain, but chemically behaves similarly to cyproheptadine.
Hypothyroidism and estrogen lengthen the QT-interval, whereas progesterone shortens it. Euthyroidism and substances including progesterone, vitamin E, niacinamide, pregnenolone, l-theanine, and aspirin dissolved in hot water with glycine and baking soda to prevent stomach irritation, along with the consumption of a diet that minimizes gut inflammation can lower anxiety.
For anxiety disorders including social anxiety disorder (SAD) and generalized anxiety disorder (GAD), some psychiatrists provide anxiolytics (anti-anxiety drugs) such as antihistamines with expectations of ECG testing to recognize cardiac (heart) abnormalities. Antihistamines can initially cause drowsiness, which can be minimized by consuming a small fraction of the therapeutic dose and titrating the dosage upwards over several weeks. Maintaining a relatively steady serum-concentration of the antihistamine through frequent dosing and careful monitoring for side effects, or taking the drug before bed can reduce variance in individual responses.
Hydroxyzine metabolizes in cetirizine, and Dr. Peat has mentioned the tendency for chlorinated carbon molecules to cause hepatic (liver) problems. Cyproheptadine by itself can inflame the liver, but neither cyproheptadine nor diphenhydramine contain chlorinated carbon molecules and therefore present a diminished risk for liver damage by this mechanism. Similarly to hydroxyzine, diphenhydramine mildly prolongs the QT-interval for cardiac repolarization.
“This multicenter, parallel (hydroxyzine [50 mg/day]; bromazepam [6 mg/day])…12 weeks of double-blind randomized treatment..Results at endpoint for percentage of responders (p =.003) and remission rates (p =.028), Clinical Global Impressions-Severity scale score (p =.001), maintenance of efficacy (p =.022), and Hospital Anxiety and Depression scale score on day 84 (p =.008) also confirmed the efficacy of hydroxyzine over placebo. The study showed no statistically significant difference between hydroxyzine and bromazepam.[a benzodiazepine drug] Except for drowsiness, which was more frequent with bromazepam, safety results were comparable in the 3 groups.
Hydroxyzine showed both efficacy and safety in the treatment of GAD and appears to be an effective alternative treatment to benzodiazepine prescription.“
Reference: Efficacy and safety of hydroxyzine in the treatment of generalized anxiety disorder: a 3-month double-blind study. – PubMed – NCBI
Posted on the Ray Peat forum: https://raypeatforum.com/community/threads/the-antihistamine-hydroxyzine-treats-anxiety.22308/#post-312835