Interactions
If diazepam is administered concomitantly with other drugs, attention should be paid to the possible pharmacological interactions. Particular care should be taken with drugs that potentiate the effects of diazepam, such as barbiturates, phenothiazines, opioids, and antidepressants.Diazepam does not increase or decrease hepatic enzyme activity, and does not alter the metabolism of other compounds. No evidence would suggest diazepam alters its own metabolism with chronic administration.Agents with an effect on hepatic cytochrome P450 pathways or conjugation can alter the rate of diazepam metabolism. These interactions would be expected to be most significant with long-term diazepam therapy, and their clinical significance is variable. Diazepam increases the central depressive effects of alcohol, other hypnotics/sedatives (e.g., barbiturates), other muscle relaxants, certain antidepressants, sedative antihistamines, opioids, and antipsychotics, as well as anticonvulsants such as phenobarbital, phenytoin, and carbamazepine. The euphoriant effects of opioids may be increased, leading to increased risk of psychological dependence. Cimetidine, omeprazole, oxcarbazepine, ticlopidine, topiramate, ketoconazole, itraconazole, disulfiram, fluvoxamine, isoniazid, erythromycin, probenecid, propranolol, imipramine, ciprofloxacin, fluoxetine, and valproic acid prolong the action of diazepam by inhibiting its elimination. Alcohol in combination with diazepam may cause a synergistic enhancement of the hypotensive properties of benzodiazepines and alcohol. Oral contraceptives significantly decrease the elimination of desmethyldiazepam, a major metabolite of diazepam. Rifampin, phenytoin, carbamazepine, and phenobarbital increase the metabolism of diazepam, thus decreasing drug levels and effects. Dexamethasone and St Johns wort also increase the metabolism of diazepam. Diazepam increases the serum levels of phenobarbital. Nefazodone can cause increased blood levels of benzodiazepines.
In humans, tolerance to the anticonvulsant effects of diazepam occurs frequently. Dependence
Improper or excessive use of diazepam can lead to dependence. At a particularly high risk for diazepam misuse, substance use disorder or dependence are:

People with a history of a substance use disorder or substance dependence Diazepam increases craving for alcohol in problem alcohol consumers. Diazepam also increases the volume of alcohol consumed by problem drinkers. People with severe personality disorders, such as borderline personality disorderPatients from the aforementioned groups should be monitored very closely during therapy for signs of abuse and development of dependence. Therapy should be discontinued if any of these signs are noted, although if dependence has developed, therapy must still be discontinued gradually to avoid severe withdrawal symptoms. Long-term therapy in such instances is not recommended.People suspected of being dependent on benzodiazepine drugs should be very gradually tapered off the drug. Withdrawals can be life-threatening, particularly when excessive doses have been taken for extended periods of time. Equal prudence should be used whether dependence has occurred in therapeutic or recreational contexts.Diazepam is a good choice for tapering for those using high doses of other benzodiazepines since it has a long half-life thus withdrawal symptoms are tolerable. The process is very slow (usually from 14 to 28 weeks) but is considered safe when done appropriately.