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Psychopharmacology in infectious diseases
1. Psychopharmacology in
Infectious Diseases
M I C H A E L T . I N G R A M , M . S . , M . D .
F E L L O W ( P G Y - 5 )
C O N S U L T A T I O N - L I A I S O N P S Y C H I A T R Y
U C L A / C E D A R S / W L A V A
2. Neuropsychiatry and Infectious Diseases
Human behavior (mobility, travel, sexual practices, substance use, etc.) interacts with Infectious
Disease risk and outcomes in complex ways
Psychiatric symptoms are part of the clinical presentation of many systemic and central nervous
system infectious processes (examples, NOT all inclusive):
HIV/AIDS
Cysticercosis
Syphilis
Toxoplasmosis
West Nile Encephalitis
Infectious diseases have been implicated in the pathogenesis of psychiatric disorders
Viral antibodies in Schizophrenia
Pediatric Autoimmune Neuropsychiatric disorder associated with streptococcal infection (PANDAS)
Lyme disease
3. Neuropsychiatry and Infectious Diseases
Pre-existing Neurological Disease, Neurological Injury, Neurocognitive impairment, and Aging
render patients more vulnerable to
Neuropsychiatric effects of even limited infectious diseases
Simple URI or UTI in young healthy individual has no major neuropsychiatric effects
But in a 78 year old woman with history of multiple CVAs and Alzheimer’s devastating delirium
Neuropsychiatric side effects of the antibiotics, antivirals, etc. used to treat infections
Reasons are unknown but thought to relate to permeability changes in blood brain barrier and
the effects of inflammatory mediators (cytokines, hormones, etc.)
An acute change in neuropsychiatric symptoms may be the first sign of impending sepsis and
may even precede the development of fever
4. Neuropsychiatry and Infectious Diseases
Psychological factors significantly affect risk for and course of infectious diseases
In a large Danish cohort of patients hospitalized for infection, 30 day mortality rate was 52% higher for
those with history of severe mental illness than those without (Ribe et al. 2015).
5. Drugs in ID: Adverse
Psychiatric Effects and
Drug Interactions
16. • Quinolones
• Increase clozapine levels
• Increase benzodiazepine levels but decreases benzodiazepine effects via
GABA receptor
• Isoniazid
• Increases haloperidol level
• Increases carbamazepine level
• If used with disulfiram can cause ataxia
• Linezolid
• Serotonin syndrome with serotonergic drugs
Antimicrobial-psychotropic drug interactions
17. Other notable interactions
• Erythromycin, Clarithromycin, and Ketoconazole
• QT prolongation and ventricular arrythmias with TCAs and
antipsychotics
• Linezolid is an irreversible MAO-A inhibitor
• Serotonin syndrome
• Hypertensive crisis
• Isoniazid is a weaker MAO inhibitor
• Reports of Serotonin syndrome and hypertensive crisis
19. HIV/AIDS
General Guidelines for prescription of psychotropic
medication to HIV patients
1. Start at lower doses and increase gradually based on tolerability
and response
2. Use the simplest possible regimen
3. Use drugs with a side effect profile that can be used as a
therapeutic advantage
4. Consider drug pharmacokinetics to minimize interactions
20. HIV/AIDS
Patients at advanced stages of liver or HIV disease have physical and cognitive impairment that
increase sensitivity to side effects
Prolonged use of antiretrovirals may lead to metabolic syndrome
Increased risk for cardiovascular and cerebrovascular diseases
Psychotropics that induce similar metabolic changes should be avoided, if possible
Examples: Olanzapine, Clozapine, Quetiapine, Valproate, Mirtazapine
Patients with a current or past history of substance dependence have greater risk of abuse of many
psychotropic drugs
Quetiapine (Suzie Qs)
Gabapentin
Bupropion (snorted)
Benzodiazepines
HIV patients have alterations in brain neurotransmitter systems (DA, 5HT)
May explain the atypical course and responses to psychiatric medications
21. HIV/AIDS
NRTIs are predominantly excreted at the kidney
Minimal interactions with psychotropics
NNRTIs have extensive metabolism via CYP450
Nevirapine, Efavirenz, Etravirine: Substrates and inducers of CYP3A4
Efavirenz and Etravirine inhibit CYP2C9 and CYP2C19
Protease Inhibitors also have extensive metabolism via CYP450
Ritonavir is most potent inhibitor of CYP3A4 > CYP2D6
CCR5 Blocker Maraviroc metabolized by CYP3A4 (not an inducer or inhibitor)
Fusion inhibitor enfuvirtide (cleared by kidney) and integrase inhibitor raltegravir (cleared via
glucuronidation) have minimal to no clinically significant interactions with psychotropics
22. HIV/AIDS and Benzodiazepines
2/3 of medications prescribed for anxiety among HIV-infected individuals are BZDs
Individuals with HIV infection are particularly sensitive to the amnesic and paradoxical effects
(disinhibition, confusion, agitation) if BZDs
Benzodiazepines of choice for HIV patients
Clonazepam
Lorazepam
Oxazepam
23. HIV/AIDS and Antidepressants
Antidepressants with the lowest CYP450 interactions are best first choice agents
Sertraline
Citalopram
Excitalopram
Venlafaxine (weak 2D6 inhibitor)
Mirtazapine
Trazodone
Bupropion (potent 2D6 inhibitor but data supporting efficacy and tolerability)
24. HIV/AIDS and Psychostimulants
Methylphenidate, Dextroamphetamine, Amphetamine salts
Used for apathy in depression
Neglect of self-care and nutrition in advanced HIV patients
Fatigue, pain, neurocognitive changes in HIV patients
25. HIV/AIDS and Mood Stabilizers
Lithium is best choice
Valproate has been used safely and has minimal CYP450 interactions
Avoid Carbamazepine
Lamotrigine has been used safely for BP depression and neuropathic pain
Metabolized by glucuronidation
Risk of SJS/TEN with rapid dose escalation
Gabapentin not a mood stabilizer but good for neuropathic pain
No hepatic metabolism
No protein binding
Pregabalin did not separate from placebo in treatment of painful HIV neuropathy
26. HIV/AIDS and Antipsychotics
HIV patients (especially late-stage) more sensitive to Extrapyramidal Symptoms (EPS)
Avoid typicals (haloperidol, chlorpromazine) due to EPS and cardiac side effects
Avoid anticholinergic agents to “prevent” EPS
Delirium risk
Cognitive decline
First line for Psychosis: Atypical Antipsychotics
Start low, go slow
No depot formulations
No clozapine or pimozide with ritonavir (increases clozapine and pimozide levels dramatically)
27. HIV/AIDS and Substance Use
Opioid Dependence
Buprenorphine better choice than methadone
Naltrexone has no CYP450 metabolism and is not expected to interact with antiretrovirals
Alcohol
Avoid Disulfiram
Used Naltrexone or acamprosate
Naltrexone: Reduces cravings, rewarding effect, and amount of alcohol consumed at relapse
Give during heavy drinking to reduce heavy drinking days
Acamprosate: Reduces cravings and attenuates relapse
Give during abstinence or early relapse