Long Acting Antipsychotic

1. Hit Me With Your Best Shot?:
A Case Series of Long‐Acting Injectable
Antipsychotic Use in HIV‐Positive Patients
Sara Siris Nash, MDa
Christina Garza, MDa
Kristin Gill, MDb
Jon Levenson, MDa
a Columbia University Medical Center, New York, NY
b SUNY Downstate Medical Center, Brooklyn, NY

2. Disclosures
• Drs. Nash, Garza, Gill, and Levenson have nothing to disclose

3. Background
• A considerable literature exists on the use of long‐acting injectable (LAI)
antipsychotics in patients with severe persistent mental illness (SPMI)
• LAI literature examines topics such as improved adherence and reductions
in relapse rates and hospitalizations
• Although there are guidelines about oral antipsychotics in HIV+ patients,
there are few controlled studies
• There has been nothing to date written about the use of LAIs in patients
with concomitant SPMI and HIV/AIDS

4. Antipsychotics and HIV/AIDS
• Psychosis in HIV can be from one of many sources
– Primary psychotic illness (eg schizophrenia)
– Resulting from other psychiatric disorders such as substance use, dementia, delirium
– Resulting from the HIV virus itself
– Resulting from opportunistic infections, especially of the CNS
– Resulting from certain anti‐retroviral medication

5. Antipsychotics and HIV/AIDS ‐ Continued
• Choice of antipsychotic must weight the pros/cons of the typicals/atypicals
in the context of HIV infection – both have potential for excellent
antipsychotic efficacy
– Typicals tend to result in greater EPS, tardive dyskinesia, and anticholinergic side effects
in HIV+ patients
– Atypicals may be better tolerated, but like the ARVs can contribute to metabolic
syndrome
– Interactions with ARVs and other medications, as well as consideration for other
underlying medical problems must be taken into account
EPS
Metabolic
Syndrome
QTc
Drug‐Drug
Interactions
Seizure
Disorder
Renal
Insufficiency
HCV

6. Long Acting Injectable vs. Oral Antipsychotics in
Schizophrenia
• Meta‐Analysis of Randomized Controlled Trials
– 2012 meta‐analysis by Kishimoto1 et al showed no significant benefit of LAIs compared with
oral antipsychotics in terms of preventing relapse of symptoms or hospitalizations
• Meta‐Analysis of Mirror Image Studies
– 2013 meta‐analysis by Kishimoto et al2 using mirrored image studies showed “strong
superiority of LAIs over oral antipsychotics in preventing hospitalization”, as well as in
decreasing the number and duration of hospitalizations
– Mirror image studies, though potentially biased (eg by expectation bias, natural illness course,
time effect) more likely reflect the average clinical patient population and real‐world
treatment than do RCTs which tend to include less sick patients, and which by their design
impose a structure that may improve adherence
1 Kishimoto T, Nitta M, Borenstein M. Long‐acting injectable versus oral antipsychotics in schizophrenia: a systematic review and meta‐analysis of
mirror‐image studies. J Clin Psychiatry 2013;74: 957‐965
2 Kishimoto T, Robenzadeh A, Leucht C et al. Long‐acting injectable vs. oral antipsychotics for relapse prevention in schizophrenia: a meta‐analysis
of randomized trials. Schizophrenia Bulletin; 2014;40:192‐213

7. Long Acting Injectable Antipsychotics
• Typicals
– Haldol decanoate
– Prolixin decanoate
• Atypicals
– Risperdal (risperidone) Consta
– Abilify (aripiprazole) Maintena
– Invega (paliperidone)
– Zyprexa (olanzapine pamoate) Relprev
• Things to keep in mind
– Side effects (EPS, akathisia, sedation syndrome)
– Frequency of injection (once vs. twice monthly)
– Drug‐drug interactions
– Need for an oral overlap period
– Cost/insurance coverage

8. Conceptualization
• Adherence can be a big problem
– Adherence to antipsychotics and anti‐retroviral treatment are critical to
successful treatment in patients with SPMI and HIV/AIDS
– 95% adherence to ARVs is necessary to result in a non‐detectable viral
load
• Hypothesis
– Optimizing adherence to antipsychotic use through the use of LAIs would
result not only in better psychiatric outcomes for patients with SPMI, but
also for improved adherence to anti‐retroviral medications

9. Methods
• Case Series
– We reviewed the experiences of 5 male patients with SPMI from the NYPH
HIV Clinic who had received at least one dose of LAI antipsychotics and
observed the effect on subsequent psychiatric and medical treatment
– Of the 5 patients observed, two received Haldol decanoate, two Risperdal
Consta, and one Abilify Maintena
– Injections of LAI occurred in multiple settings, including the outpatient
clinic, inpatient medical hospital, and inpatient psychiatric hospital

10. Case 1: Mr. R
• Mr. R is a 39 y/o Hispanic man with AIDS (CD4 of 1, VL 2.8M copies), non‐
adherent with ARVs, numerous opportunistic infections including PCP
pneumonia, CMV colitis, candidiasis, as well as MRSA skin
lesions/abscesses/ bacteremia
• Psych history is “pan‐positive” for psychotic, mood, and anxiety symptoms
an extensive substance use (alcohol, intranasal cocaine, crack, heroin), as
well as a significant history of violence with lengthy incarcerations
suggestive of a primary antisocial personality disorder
• Numerous CPEP visits and inpatient admissions throughout NYC during
which he would be treated with antipsychotics, benzodiazepines, opioids,
antidepressants, and mood stabilizers
• Routinely missed outpatient visits, and reconnected with psychiatry during
medical admissions

11. Case 1: Mr. R ‐ Continued
• In 2/2013 Mr. R was admitted to the ID service for the treatment of
chronic pancreatitis
• He was incidentally found to have a right gluteal intramuscular collection
(7.0 x 2.3 cm) with rim enhancement on CT concerning for an abscess;
fluid was drained and found to be consistent with a non‐infected seroma
• Mr. R reported having received a Haldol Decanoate injection (150 mg) at
the site in question during an inpatient psychiatric admission elsewhere in
the city in 1/2013

13. Case 2: Mr. S
• Mr. S is a 47 y/o Jamaican man with AIDS (CD4 8, VL 16K), non‐adherent
with ARVs, several past opportunistic infections
• Psychiatric history is significant for longstanding psychotic illness, most
likely schizophrenia (vs. schizoaffective disorder) as well as extensive
substance abuse (primarily cocaine, also alcohol and marijuana)
• He has had numerous psychiatric admissions for decompensated
psychosis, including command auditory hallucinations and suicidal
ideation, in the context of antipsychotic non‐adherence and substance use

14. Case 2: Mr. S ‐ Continued
• During a lengthy medical admission on the infectious disease service in
6/2013, Mr. S was followed by the CL service for depression and psychosis
in the context of stopping his risperidone and using crack
• He was restarted on risperidone to 6 mg at bedtime
• Given his tumultuous history, he was encouraged to try LAI risperidone,
and received his first 25 mg injection in the hospital, which he tolerated
well, and was prescribed oral risperidone for the cross‐over period
• He did not follow up for subsequent injections at the outpatient clinic, and
ultimately presented to the CPEP 3 months later off all antipsychotics and
requesting drug rehab
• He continued to avoid psychiatric follow up, but was restarted on oral
risperidone by his PMD; as of summer 2014, he had been clean from drugs
and adherent to his oral psychotropics

15. Case 3: Mr. H
• Mr. H is a 44 y/o African American man with HIV (CD4 760, VL <20 – 77)
• Psychiatric history is significant for schizophrenia with lengthy period of
state hospitalization, past court mandated outpatient treatment, past
cocaine and marijuana use, and historic medication non‐adherence
• Though initially at least partially adherent to risperidone and valproic acid,
he decompensated in 4/2013 resulting in several psychiatric admissions to
various city hospitals
• During a 6/2013 admission he refused day treatment placement; return to
our clinic was contingent on his agreeing to a trial of LAI risperidone
• He received one injection prior to hospital discharge but did not follow up
as an outpatient
• Over the past year he has had several more psychiatric admissions, as well
as unstable housing; he has not returned to outpatient psychiatric care,
and only rarely follows with his medical provider

16. Case 4: Mr. J
• Mr. J is a 61 y/o Haitian man with AIDS (CD4 8, VL 315K), non‐adherent to
ARVs, with numerous past opportunistic infections including PCP
pneumonia, and esophageal candidiasis, as well as TB
• Psychiatric history is significant for chronic persecutory delusions of
people trying to harm or kill him through Voodoo; he also maintains
delusions about not having HIV
• In 7/2013 he was admitted to the medical hospital with c.difficile colitis
and was found to be paranoid and delusional
• CL psychiatry treated with risperidone, changed to haloperidol with good
effect on psychosis, however pt developed profound EPS; he was
ultimately transitioned to aripiprazole, and was transferred to inpatient
psychiatry

17. Case 4: Mr. J ‐ Continued
• Aripiprazole was titrated to 30 mg/day with profound effect on his
psychotic symptoms, including his delusions about HIV/AIDS and his
willingness to take ARVs
• Prior to discharge from inpatient psychiatry, Mr. J was given an injection of
Abilify Maintena 300 mg with the hope it would help combat past poor
adherence to both psychotropics and ARVs; he was also continued on oral
aripiprazole for the cross‐over
• He stopped the oral medication immediately, and returned to the ED 6
days after discharge from psychiatry with altered mental status
characteristic of delirium, as well as renewed paranoid delusions of having
been kidnapped; medically he was found to have a decubitus ulcer
• He was restarted on oral aripiprazole as well as on his ARVs and was
ultimately discharged to a skilled nursing facility; he has not subsequently
followed up in our clinic

18. Case 5: Mr. C
• Mr. C is a 53 y/o Hispanic man with HIV (CD4 530, VL <20), HCV with
cirrhosis and HCC
• Psychiatric history is significant for schizophrenia, past substance abuse
(cocaine, IV heroin, marijuana)
• First encounter was in 2011 when he thought I was the liver transplant
psychiatrist; at that time he was stable on Haldol decanoate 100 mg
monthly at another center
• In 10/2012 he transferred care to our clinic, but we could not obtain
Haldol decanoate; he was maintained on Haldol 5 mg PO bid
• In 2/2013 in the context of his mother’s death and inconsistent adherence
to oral Haldol, he became floridly psychotic – disorganized, and convinced
that he was Jesus Christ

19. Case 5: Mr. C ‐ Continued
• Mr. C was psychiatrically hospitalized and restarted on his Haldol
decanoate 150 mg
• He has been adherent with the monthly injections, though developed
akathisia and his dose had to be reduced to 100 mg
• Mr. C is currently at a stable baseline psychiatrically; his current main
problem is his severe liver disease

20. Conclusions
• If you’re going to fail, fail BIG?
– Our initial hypothesis suggesting improved adherence would follow LAI treatment
proved incorrect
– 4 of 5 patients received only a single dose of LAI; in these patients ARV adherence was
variable; these four all effectively dropped out of psychiatric care
– The 5th patient was restabilized on his LAI, and continued to take his ARVs
• How wrong were we?
– What can we really tell from single dose LAIs, especially when non‐adherence occurred
with the oral overlap period?
– Very small sample size in this observational case series

21. Conclusions ‐ Continued
• Special considerations in the HIV/AIDS population
– Degree of illness: does severe immunocompromise place patients at a higher risk of
adverse effects?
• Infectious complications?
• Delirium?
• Other issues for consideration
– “Psychosocial issues” have been shown to have an effect on adherence; this was
observed in our case series as well
• Substance abuse/dependence
• Unstable support mechanisms, including housing
• Selectivity of non‐adherence?
– Non‐adherence to LAIs, and intermittent adherence with oral antipsychotics reflects
patterns seen in the general population of patients with SPMI
– However, despite non‐adherence to antipsychotics, some of these patients maintain
fairly good adherence to their ARVs

22. Looking to the Future
• Ongoing exploration of LAI use in patients with HIV/AIDS is warranted
• The only way we will come to further conclusions, is by ongoing work with
our best teachers ‐ our patients