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People with mental health problems—especially those with schizophrenia—are also prone to abuse the drug, which is self-administered in large doses to treat extrapyramidal symptoms caused by the use of antipsychotics.

A study conducted on adult males with a history of sedative abuse found that subjects who were administered a high dose (400mg) of diphenhydramine reported a desire to take the drug again, despite also reporting negative effects, such as difficulty concentrating, confusion, tremors, and blurred vision.

Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Two to 4 weeks is generally adequate, but some patients may need the adjunctive therapy for several months. Aripiprazole: a dopamine-serotonin system stabilizer [abstract no.

Long-term anticholinergic use is associated with an increased risk for cognitive decline and dementia among older people.

Several levels of evidence strongly indicate diphenhydramine (similar to chlorpheniramine) can block the delayed rectifier potassium channel and, as a consequence, prolong the QT interval, leading to cardiac arrhythmias such as torsades de pointes. Like many other first-generation antihistamines, diphenhydramine is also a potent antimuscarinic (a competitive antagonist of muscarinic acetylcholine receptors) and, as such, at high doses can cause anticholinergic syndrome.

The drug is an ingredient in several products sold as sleep aids, either alone or in combination with other ingredients such as acetaminophen (paracetamol). Diphenhydramine can cause minor psychological dependence. Topical diphenhydramine is sometimes used especially for people in hospice.

This use is without indication and topical diphenhydramine should not be used as treatment for nausea because research does not indicate this therapy is more effective than alternatives. This activity is responsible for the side effects of dry mouth and throat, increased heart rate, pupil dilation, urinary retention, constipation, and, at high doses, hallucinations or delirium.

Diphenhydramine can be quantified in blood, plasma, or serum.

This discovery led to a search for viable antidepressants with similar structures and fewer side effects, culminating in the invention of fluoxetine (Prozac), a selective serotonin reuptake inhibitor (SSRI). FDA has required special labeling warning against use of multiple products that contain diphenhydramine.

Intramuscular ziprasidone compared with intramuscular haloperidol in the treatment of acute psychosis.

Delayed-onset hypothesis of antipsychotic action: a hypothesis tested and rejected.

A 1985 review of antihistamine pharmacokinetics found that the elimination half-life of diphenhydramine ranged between 3.4 and 9.3 hours across five studies, with a median elimination half-life of 4.3 hours. Analogues of diphenhydramine include orphenadrine, an anticholinergic, nefopam, an analgesic, and tofenacin, an antidepressant.

The selective serotonin reuptake inhibitor (SSRI) antidepressant fluoxetine is also a close analogue of diphenhydramine.

Collaborative Working Group on Clinical Trial Evaluations.

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