In today's modern society, it seems to be more and more challenging to cope with life stresses. The effect of psychological stress on emotional and physical health can be devastating, and increased stress is associated with increased rates of heart attack, hypertension, obesity, addiction, anxiety and depression. This review focuses on the possibility of an influence of psychological stress on the metabolism of selected antidepressants (TCAs, SSRIs, SNRIs, SARIs, NDRIs a MMAs) and anxiolytics (benzodiazepines and azapirone), as patients treated with antidepressants and/or anxiolytics can still suffer from psychological stress. Emphasis is placed on the drug metabolism mediated by the enzymes of Phase I, typically cytochromes P450 (CYPs), which are the major enzymes involved in drug metabolism, as the majority of psychoactive substances are metabolized by numerous CYPs (such as CYP1A2, CYP2B6, CYP2C19, CYP2C9, CYP2A6, CYP2D6, CYP3A4). As the data on the effect of stress on human enzymes are extremely rare, modulation of the efficacy and even regulation of the biotransformation pathways of drugs by psychological stress can be expected to play a significant role, as there is increasing evidence that stress can alter drug metabolism, hence there is a risk of less effective drug metabolism and increased side effects.

• Keywords
• antidepressants, anxiolytics, cytochrome P450, drug metabolism, psychological stress,
• MeSH
• Antidepressive Agents metabolism   MeSH
• Anti-Anxiety Agents * metabolism   MeSH
• Biotransformation MeSH
• Microsomes, Liver metabolism   MeSH
• Humans MeSH
• Stress, Psychological MeSH
• Cytochrome P-450 Enzyme System metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Antidepressive Agents MeSH
• Anti-Anxiety Agents * MeSH
• Cytochrome P-450 Enzyme System MeSH

Clonazepam is long-acting benzodiazepine agonist used in short-acting benzodiazepine withdrawal; however, recent observations suggest the existence of its abuse. We demonstrate a 40-year-old man with a 20-year history of psychiatric care with recently benzodiazepine dependence (daily intake of ∼60 mg of clonazepam and 10 mg of alprazolam). High serum levels of both drugs were analyzed 3 weeks before admission to hospitalization (clonazepam 543.9 ng/mL, alprazolam 110 ng/mL) and at the time of admission (clonazepam 286.2 ng/mL, alprazolam 140 ng/mL) without any signs of benzodiazepine intoxication. Gradual withdrawal of clonazepam with monitoring of its serum levels and increase of gabapentin dose were used to minimize physical signs and symptoms of clonazepam withdrawal. Alprazolam was discontinued promptly. Clinical consequences of the treatment were controllable tension, intermittent headache, and rarely insomia. It is the first case report showing utilization of therapeutic drug monitoring during withdrawal period in the patient with extreme toleration to severe benzodiazepine dependence.

• MeSH
• Substance Withdrawal Syndrome etiology   MeSH
• Adult MeSH
• GABA Modulators administration & dosage   adverse effects   blood   MeSH
• Clonazepam administration & dosage   adverse effects   blood   MeSH
• Humans MeSH
• Drug Monitoring * MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH
• Names of Substances
• GABA Modulators MeSH
• Clonazepam MeSH