Medication-Assisted Psychotherapy: The

Past and Future of Psychiatry

Jan 12, 2024
By Ioannis Alex Malidelis, MD
Andrew Hunt, MD
View All
Publication Article
Psychiatric Times Vol 41, Issue 1

ART STOCK CREATIVE/AdobeStock

Psychiatric practice has increasingly relied on medication

management rather than psychotherapy as a mainstay of treatment
over the past few decades, despite the general recognition that
pharmacology alone is insufficient for most patients. Combined
pharmacological and psychosocial treatment, therefore, remains the
optimal goal of psychiatry care. In addition, the growth of public
interest in this area and the explosion of new research around
psychedelics indicate an important place for combined treatments in
the near future of clinical psychiatry. The questions for clinicians
have become: How can we understand medication and
psychotherapy and their interactive potential, and how can
medication be understood and employed as a tool to enhance
progress in the context of psychotherapy? To best answer these
questions, we need a better understanding of the literature on
combined medication-psychotherapy and medication-assisted
psychotherapy.

Pharmacology and psychotherapy have been combined in recent

literature in the use of fast-acting psychoactive compounds to
augment an intensive session of psychotherapy. This strategy is
known as medication-assisted psychotherapy (MAP), substance-
assisted psychotherapy (SAPT), and psychedelic psychotherapy
(PAP), depending on the medicine utilized and the context in which it
is given. The literature lacks a clear consensus on the exact definition
of these terms and what differentiates each term from the other.

Articles in this issue

"Lay Down Sally" Exploring the Ro

Brexpiprazole in
Alzheimer Deme
Agitation

For the sake of consistency, we will use MAP to describe any

combination of medication and psychotherapy, including
conventional psychotropics, such as selective serotonin reuptake
inhibitors (SSRIs) when the goal of medication use is to facilitate and
enhance the psychotherapy process, and we will use PAP to describe
faster-acting mind-altering substances, ie, typical and atypical
psychedelics (eg, 3,4-methylenedioxymethamphetamine [MDMA],
ketamine, psilocybin, LSD, ibogaine), used during intensive
psychotherapeutic sessions. Psychedelics are currently being
investigated in clinical trials in conjunction with the delivery of a
psychological intervention with the aim of treating specific
psychiatric conditions.

Historical Background

Psychiatry has stood apart as a medical specialty because of the

distinctive emphasis on psychotherapy as a treatment modality. In
the middle decades of the 20th century, psychoanalysis was the
dominant paradigm in American psychiatry and the main approach
for the treatment of psychiatric disorders. The pharmacological
revolution began in the 1950s and 1960s when pharmacological
treatments for major psychotic, mood, and anxiety disorders were
developed and popularized. In these early decades, however,
pharmacology was commonly employed as an adjunct to facilitate
psychotherapy, and this attitude is reflected in the pharmaceutical
advertisements of the era.1 For example, an early ad for Elavil
(amitriptyline) noted2:

The psychiatrist’s office still represents the setting in which the

psychoanalytic process recognizes its fullest potential. Frequently, however,
an antidepressant must be employed to foster a working therapeutic
relationship. With effective symptomatic relief often provided by Elavil,
depressed patients may be able to concentrate on underlying factors
instead of somatic manifestations.

Read more

Psychotherapy Mood Disorders Psychopharmacology PTSD

Psychedelics Depression Major Depressive Disorder

This attitude toward medication use in the context of psychotherapy

began to change in the 1990s with the popularization of SSRIs, which,
due to their improved tolerability, allowed primary care physicians to
prescribe (typically without therapy). Simultaneously, the influence of
managed care on US health care made integrated treatment less
feasible. Since then, there has been a steady decline in the amount of
psychotherapy offered by psychiatrists. A 2021 study found that
between 1996 and 2016, the percentage of psychiatric visits involving
psychotherapy had decreased by half, dropping to 21.6% of patient
visits in 2016.3 This number is likely to have dropped even further
since then.

Interestingly, psychiatric training has protected its insistence upon

psychotherapy as a competency for resident trainees. Many
psychiatrists still identify as psychotherapists, and pride themselves
on their mastery of both psychological and pharmacological
treatment approaches. Psychiatric clinicians have a uniquely
comprehensive capacity in the treatment of psychiatric patients, as
they are the only group of mental health care professionals
authorized to provide integrative pharmacotherapy and
psychotherapy.

As readers know, a fully integrated approach, in which a single

clinician offers both pharmacotherapy and psychotherapy, has
several advantages, including enhanced continuity of care, improved
communication, coordination between treatment modalities, and
increased convenience for patients. This integrated approach also
allows for a comprehensive understanding of the patient’s condition
and the ability to tailor treatment to individual needs.
However, there are also potential disadvantages to this approach,
which have likely contributed to its decline. Clinicians may face
challenges in maintaining proficiency in both pharmacotherapy and
psychotherapy due to the extensive training required for each.
Additionally, time constraints may limit the depth and quality of each
treatment modality, and financial pressures may incentivize
psychiatrists to focus more of their time on medication management
alone.

Historical Insights

The use of psychoactive compounds during psychotherapy has an

extensive historical basis in psychiatry going at least as far back as
the 1930s when William J. Bleckwenn, MD, started conducting
experiments with subanesthetic doses of amylobarbitone in
combination with analytic techniques.4 Bleckwenn demonstrated the
potential of drug-assisted interviews in psychiatry and laid the
foundation for further advancements in the field of barbiturate-
assisted interviews and their application in psychiatric treatment.
During World War II, the use of barbiturate-assisted interviews
experienced a significant surge. The technique was particularly
employed to facilitate abreaction, the release of previously repressed
emotions, especially in the treatment of posttraumatic stress
disorders (PTSDs). The enthusiasm for barbiturate-assisted
interviews continued in civilian practice after the war, via various
techniques including prolonged narcosis and narco-hypnoanalysis.
However, by the early 1960s, the technique began to decline, mostly
due to concerns about barbiturate dependence, the introduction of
new psychiatric medications such as chlorpromazine and tricyclic
antidepressants, and the popularity of hallucinogenic drugs (eg,
LSD).4

Psychodynamic Psychopharmacology

Psychodynamic psychopharmacology is an approach that seeks to

integrate the principles of psychodynamic theory with pharmacology.
This area of research has emerged as an important approach to
mental health treatment and has played an important role in the
development of combined pharmacological and psychotherapeutic
interventions. Psychodynamic psychopharmacology recognizes the
role of meaning, psychosocial factors, and interpersonal dynamics in
treatment-refractory mental illnesses. It highlights that psychosocial
factors and the patient-doctor relationship are often overlooked in
psychiatric treatment, leading to treatment resistance and limited
outcomes. This is achieved by recognizing the importance of the
integration of biological psychiatry and psychodynamic insights
(Table 1). By incorporating psychodynamic principles into
psychopharmacological practice, psychiatrists can better understand
and address the complex psychological factors that influence
treatment outcomes. This approach enhances the integration of
meaning and biology, leading to more effective and patient-centered
care for individuals with treatment-resistant mental illnesses.5,6

Table 1. The 6 Primary Principles of Psychodynamic Psychopharmacology

Combined Treatment

Comparative efficacy trials over the past few decades have provided
evidence that a combination of psychotherapy with
psychopharmacology together are more efficacious than either alone
for a variety of diagnoses,7-10 with psychotherapy and medication
differing in treatment efficacy for various target symptoms, having
different rates of action, or enhancing duration of effective
treatment.11,12 Moreover, because contemporary hypotheses around
the mechanism of action of antidepressants center on
neuroplasticity,13 this again suggests a vital role for psychosocial
treatments to provide optimal learning environment for, to use a
common metaphor, “rewiring of the brain” (Table 2). Thus, the
plausibility of synergistic independent complementary effects of
combined medication and psychotherapy is supported by clinical and
neuroscientific literature.
 Table 2. Hypothesized Mechanisms of Pharmacological Action and Psychotherapeutic Facilitation

Propranolol-Assisted Psychotherapy

The use of propranolol in conjunction with psychotherapy for PTSD

began gaining attention after research in the 1980s postulated that
epinephrine and norepinephrine play a role in formation of traumatic
memories in PTSD.14

A β-blocker, propranolol acts as a competitive antagonist to inhibit

catecholamines, so it was hypothesized that it might have
therapeutic efficacy for the prevention and treatment of PTSD.
Research investigating the use of propranolol has primarily focused
on 2 main indications:

1. Use after the immediate experience of traumatic events to prevent

consolidation of traumatic memories.

2. Given in combination with trauma therapy to reactivate traumatic

memories. Propranolol was theorized to interfere with the
reconsolidation process and weaken the emotional intensity
associated with traumatic memories.15

Clinical studies have been conducted to investigate the efficacy of

propranolol-assisted psychotherapy for PTSD. These studies involved
administering propranolol prior to or after psychotherapeutic
sessions, such as exposure therapy or cognitive-behavioral therapy.
One of the earliest studies investigated the effects of propranolol in
reducing the intensity of traumatic memories during therapy sessions
for Vietnam combat veterans with chronic PTSD. The researchers
found propranolol administration prior to therapy sessions led to a
significant reduction in subjective distress associated with traumatic
memories.16 Although a 2018 systematic review did not show any
significant evidence that propranolol was effective for traumatic
memory disruption in patients with PTSD, likely due to small sample
sizes and heterogeneity of dosages as limitations,17 another study
showed that the combination of propranolol and reconsolidation
blockade (RRB) therapy led to a significant reduction in PTSD
symptoms compared with placebo plus RRB therapy, indicating a
potential synergistic effect of the combined treatment approach.18

MDMA
Recently MDMA has been investigated as a treatment for PTSD in the
context of psychotherapy, with the US Food and Drug Administration
granting breakthrough therapy designation for MDMA-assisted
therapy for PTSD in 2017. The first phase 3 findings were published in
2021 with promising results.19 In the study, participants with severe
PTSD were randomly assigned to receive either manualized therapy
with MDMA (n=46) or with placebo (n = 44) at 1 of 15 study sites
across the United States, Canada, and Israel. Participants underwent
three 8-hour experimental sessions spaced 4 weeks apart with a
single divided dose of 80 to 180 mg MDMA or placebo, in addition to
3 preparatory and 9 integrative therapy sessions.

In the first experimental session, participants received an initial dose

of 80 mg followed by a supplemental half-dose of 40 mg, 1.5 to 2.5
hours later. In the second and third experimental sessions,
participants received an initial dose of 120 mg followed by a
supplemental half-dose of 60 mg. Each experimental session was
followed by three 90-minute integrative sessions spaced 1 week
apart to allow participants to incorporate their experiences. At the
primary end point at 18 weeks, 67% of participants in the MDMA
group no longer met diagnostic criteria for PTSD, compared with 32%
of participants in the placebo group.19 Positive results from a second
phase 3 trial have also been reported.20

MDMA is thought to work by reducing the emotional intensity

associated with traumatic memories by reconsolidating traumatic
memories during psychotherapy in a way that they are stored with
less excitatory activation.21 MDMA has also been noted to increase
feelings of trust, safety, and empathy, possibly mediated via release
of oxytocin and serotonin, which can improve the therapeutic alliance
between the therapist and individual.22,23

Psilocybin

Although psilocybin has been studied in conjunction with

psychotherapy for several psychiatric diagnoses including nicotine
dependence, alcohol dependence, obsessive-compulsive disorder,
cluster headache, cancer-related existential distress, and anxiety
disorders, much of the research has focused on the treatment of
patients with a diagnosis of treatment resistant depression.23

Several phase 2 trials have shown the potential efficacy of psilocybin-

assisted psychotherapy for the treatment of patients with treatment
resistant depression and, in 2018, the FDA granted breakthrough
therapy designation for psilocybin-assisted therapy for treatment-
resistant depression. One of the phase 2 studies involved 24 patients
with major depressive disorder who received either a single dose of
psilocybin or a placebo in a therapeutic setting and were followed for
4 weeks after treatment.24 The results showed that psilocybin-
assisted therapy led to significant reductions in depression
symptoms as measured by the Hamilton Depression Rating Scale
(HAM-D). At 1 week after treatment, the mean HAM-D score was
significantly lower in the psilocybin group compared with the placebo
group (8.0 vs 14.4). At 4 weeks post treatment, the psilocybin group
still showed a significant reduction in mean HAM-D scores compared
with baseline (10.9 vs 22.8), whereas the placebo group did not (19.3
vs 21.7). A prospective 12-month follow-up found that psilocybin-
assisted therapy resulted in significant improvements in depressive
symptoms at 1 week, 4 weeks, and 12 months after treatment, with
the mean HAM-D scores decreasing from 22.8 at baseline to 8.0 at 1
week, 8.5 at 4 weeks, and 9.8 at 12 months after treatment.25

Additional Considerations

As opposed to medication management outside therapeutic context,

there is an added importance on the type of experience during the
PAP sessions. Specifically, mystical experiences, meaningful insights,
and belief changes have frequently been cited as predictive of
positive outcomes of psychedelic trials because they enable
individuals to transcend their usual patterns of thinking, feeling, and
acting.26,27 These experiences can increase insightfulness,
introspection, divergent thinking, and mindfulness-related capacities;
reduce avoidance; and induce emotional breakthrough experiences
that can help resolve existential distress.27

In PAP, set and setting is thought to have a large impact on the

outcomes of the therapies. Set refers to the individual’s mind-set, or
the internal attitudes, expectations, and psychological state that they
bring into the therapeutic experience. Setting, on the other hand,
refers to the physical, social, and cultural environment where the
therapy takes place. It covers the comfort and safety of the physical
surroundings, the presence and demeanor of the therapist(s), and the
broader societal and cultural attitudes toward psychedelics and
mental health. A supportive, calm, and comfortable setting is
essential to facilitate a positive therapeutic experience.

Neurophysiological and Psychological Views

The integrated use of medications to facilitate psychological

recovery breaks down the dichotomy between the neurophysiological
and psychological views. Mental processes, after all, are the product
of physical brain activities. Experiences and environments can
produce long-standing neurophysiological changes, recognized by
phenomena such as neuroplasticity and epigenetics.28 Psychiatric
medications instigate a cascade of neurotransmission involving key
neurochemicals such as serotonin, dopamine, norepinephrine,
glutamate, and oxytocin. These neurochemical alterations function
as potent facilitators of neuroplasticity, serve to attenuate amygdala
reactivity during emotional processing, and instigate reductions in the
activity of the default mode network. The ensuing psychological
alterations are multifaceted, encompassing an attenuation of fear
responses and feelings of shame, augmented emotional empathy,
enhanced processing of traumatic memories, and a marked increase
in openness and interpersonal trust.29 Neurophysiological activity
underlies psychological experiences, whereas psychological factors
influence neurophysiological functioning. Recognizing their
interdependence is crucial for a comprehensive understanding of
mental health and a convergence toward a common understanding.

Concluding Thoughts

A substantial body of literature supports the efficacy of combining

medications, illustrated in this narrative review by conventional
medications such as SSRIs and propranolol as well as psychoactive
compounds such as MDMA and psilocybin, with psychotherapeutic
interventions for treatment of many psychiatric conditions. MAP
recovers and reintroduces an emphasis on using the experiential
aspect of psychotropics to enhance progress in psychotherapy. Many
methodological challenges remain regarding the clinical study of
psychedelics (see van Elk and Fried30) but available results are
promising.

Research evidence continues to indicate the additional benefits of the

synergistic use of medication with psychotherapy. As opposed to the
currently dominant model of medication as the primary treatment
modality, many of these approaches emphasize the importance of
the experience itself and point to the ways in which medications alter
the neurobiology to facilitate neuroplasticity, learning, and behavioral
modifications.

It is the responsibility of all psychiatric clinicians to familiarize

themselves with integrative treatment for the benefit of their patients.
Our expertise in both the pharmacological and psychological aspects
of patient care will be key to providing the best care possible.

Dr Malidelis is PGY4 at Case Western Reserve University, University

Hospitals Cleveland Medical Center, Adult Psychiatry Residency
Program, Cleveland, Ohio. Dr Hunt is assistant program director, Case
Western Reserve University, University Hospitals Cleveland Medical
Center, Adult Psychiatry Residency Program. Dr Aftab is clinical
assistant professor, Department of Psychiatry, Case Western Reserve
University School of Medicine. He also is a member of the Psychiatric
Times Editorial Board. All authors report no conflicts of interest and
have no disclosures to report.

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the effects of psychotherapies, pharmacotherapies and their
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efficacy of antidepressant medication vs. cognitive behavioral
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16. Pitman RK, Sanders KM, Zusman RM, et al. Pilot study of
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21. Jerome L, Feduccia AA, Wang JB, et al. Long-term follow-up

outcomes of MDMA-assisted psychotherapy for treatment of PTSD: a
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24. Davis AK, Barrett FS, May DG, et al. Effects of psilocybin-assisted
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Download Issue PDF

Exploring the Role of Brexpiprazole in

Alzheimer Dementia Agitation
Jan 16, 2024
By Justin Allen, MD
Albert Dickan, MD
View All

News Article

How efficacious is brexpiprazole as a treatment for agitation associated with Alzheimer

disease?
 yurakrasil_AdobeStock

TRANSLATING RESEARCH INTO PRACTICE

Rajesh R. Tampi, MD, MS, DFAPA, DFAAGP, Column Editor

This is the first of a monthly column dedicated to reviewing the

literature and sharing clinical implications.

In May 2023, brexpiprazole (Rexulti) became the first medication to

receive supplemental approval from the FDA for the treatment of
agitation associated with dementia due to Alzheimer disease (AD).
Its effectiveness for this indication was determined through two 12-
week, randomized, double-blind, placebo-controlled, fixed-dose
studies.

This particular study was chosen as it is the second of the 2 studies

that evaluated its effectiveness for treatment of agitation associated
with dementia due to AD; it was recently published in a leading
scientific journal.

Study

Read more

Alzheimer Disease Dementia Psychopharmacology

Lee D, Slomkowski M, Hefting N, et al. Brexpiprazole for the treatment

of agitation in Alzheimer dementia: a randomized clinical trial. JAMA
Neurol. Published online November 6, 2023.1

Study funding

Otsuka Pharmaceutical Development & Commercialization, Inc; and

H. Lundbeck A/S
Study objectives

To determine the efficacy, safety, and tolerability of brexpiprazole for

the treatment of agitation in patients with AD.

Methodology

This study was a 12-week randomized, phase 3, double-blind,

placebo-controlled trial that ran from May 2018 to June 2022.
Patients were screened at 123 AD clinical trial sites in Europe and the
United States.

There were 3 requirements to meet the diagnosis of AD: (1) diagnosis

based on National Institute of Neurological and Communicative
Disorders and Stroke and the Alzheimer’s Disease and Related
Disorders Association (NINCDS-ADRDA) criteria; (2) screening and
baseline Mini-Mental State Examination scores between 5 and 22;
and (3) brain imaging consistent with an AD diagnosis.

To meet the definition of agitation, the requirements included

meeting the International Psychogeriatric Association definition for
agitation, onset of symptoms at least 2 weeks prior to screening, an
agitation/aggression score of 4 or greater on the Neuropsychiatric
Inventory (NPI) or NPI–Nursing Home Version (NPI-NH) at screening
and baseline, and positive Cohen-Mansfield Agitation Inventory
(CMAI) factor 1 criteria.

Other key inclusion criteria included age of 55 to 90 years, the need

for pharmacotherapeutic intervention based on investigator
judgment, living in a community-based setting or care facility, and
having an identifiable caregiver. Pertinent exclusion criteria included
memory impairments due to reasons other than AD and clinically
significant and symptomatic neurological, psychiatric, or other
unstable medical comorbidities.

Participants were randomly assigned using a computer model to the

brexpiprazole and placebo arms in a 2:1 ratio. Individuals in the
brexpiprazole arm were further randomly assigned to receive 2 or 3
mg/day of medication in a 1:2 ratio. Participants, caregivers,
investigators, and sponsors were blinded to randomization. Study
drugs were administered at the same time once per day, and patient’s
visited clinical trial sites once every 2 weeks for progressive
assessment.

Efficacy was measured by change in CMAI total scores from baseline

to week 12, the clinician-rated Clinical Global Impression Severity of
illness (CGI-S) and Improvement (CGI-I) scales specifically applied to
agitation, and the NPI-NH. Safety was assessed by treatment-
emergent adverse events (TEAEs), routine vital signs, weights,
laboratory testing, the Sheehan Suicidality Tracking Scale, the MMSE,
and 3 extrapyramidal symptom scales.

Study Results

A total of 345 participants at 68 sites across 7 countries (United

States, Ukraine, Bulgaria, Serbia, Slovakia, Spain, and Hungary)
enrolled. Participants were randomly assigned as follows: 75 to
brexpiprazole 2 mg/day, 153 to brexpiprazole 3 mg/day, and 117 to
placebo. Two participants in the brexpiprazole 2-mg group and 1 in
the placebo group did not receive treatment and were not included in
the safety and efficacy samples.

Baseline demographic and clinical characteristics were similar

across the groups. The mean age was 74.5 years in the brexpiprazole
group and 73.0 years in the placebo group. A total of 93.9% of
participants in the brexpiprazole group and 98.3% in the placebo
group were White.

Study completion rates were 88.9% in the placebo group and 86.8% in
the brexpiprazole groups (90.7% and 85.0% for the brexpiprazole 2-
mg/day 3-mg groups, respectively). Discontinuation rates due to
adverse events were 4.3% in the placebo group and 5.3% in the
brexpiprazole groups (1.4% and 7.2% in the brexpiprazole 2-mg and 3-
mg groups, respectively.

The mean difference in CMAI total scores at week 12 was –22.6 from
baseline in the brexpiprazole groups, whereas the placebo group had
a change of –17.3 from baseline (difference of −5.32; 95% CI, −8.77
to −1.87; P = .003; effect size = 0.35). All other secondary efficacy
end point measures (CGI-S, CGI-I, CMAI subscale scores and
response rates, and NPI-NH) also showed statistically significant
greater improvement in the brexpiprazole group compared with
placebo.

For the CGI-S score as related to agitation, there was a mean

difference of –1.2 for the brexpiprazole group compared with a –0.9
mean difference in the placebo group (difference of –0.27; 95% CI, –
0.47 to –0.07; P = .008; effect size = 0.31).

However, when looking at the brexpiprazole subgroups, only the 3-mg

group showed statistically significant improvement in the CGI-S
score. The CGI-I mean score for the brexpiprazole group at the end of
12 weeks was 2.7, whereas the placebo group had a mean score of
3.0 (difference of –0.33; 95% CI, –0.57 to –0.09; P = .007). The NPI-
NH total score in the brexpiprazole group showed a mean difference
of –17.3 from baseline compared with –12.7 for placebo (difference
of –4.60; 95% CI, –7.33 to –1.88; P = .01; effect size = 0.39).
Less than half (40.7%) of participants reported at least 1 TEAE in the
brexpiprazole group vs 31% in the placebo group. The TEAEs with an
incidence of greater than or equal to 2% occurred with more
frequency in the brexpiprazole vs placebo group (Figure).

Figure. Percentage of TEAEs in Brexpiprazole vs Placebo

The mean change in body weight was +0.3 kg for the brexpiprazole
group; there was no mean change in body weight in the placebo
group.

Rates of weight gain of 7% or more from baseline were 1.5% in the

brexpiprazole group and 0.0% in the placebo group. Rates of weight
loss of 7% or more from baseline were 1.0% for both the
brexpiprazole and placebo groups.

Conclusions

Evidence from this high-quality, 12-week randomized, double-blind,

and placebo-controlled trial indicated that brexpiprazole at fixed
doses of 2 or 3 mg/day is more efficacious than placebo at reducing
agitation associated with AD. Similarly, brexpiprazole at these doses
is well tolerated.

Practical Applications

Among older adults who exhibit agitation associated with AD,

brexpiprazole is an efficacious and well-tolerated treatment option.
Based on this trial’s data and the published data from 1 of the 2 prior
trials,3 brexpiprazole was the first medication to receive FDA approval
for the treatment of agitation associated with dementia due to AD.

Bottom Line

This high-quality phase 3 trial indicated that brexpiprazole (at 2 and 3

mg/day) is more efficacious than placebo in treating AD-associated
agitation over 12 weeks. Brexpiprazole was generally well tolerated
when compared with placebo; headache was the most commonly
reported adverse effect in both groups. Brexpiprazole was also
associated with a mild increase in sedation and no statistically
significant difference in weight gain or extrapyramidal symptoms.

Dr Allen and Dr Dickan are second-year psychiatry residents at

Creighton University School of Medicine in Omaha, Nebraska. Dr Woo
is a first-year psychiatry resident at Creighton University. Dr Mullen is a
fourth-year psychiatry resident at Creighton University. Dr Tampi is
professor and chairman in the Department of Psychiatry at Creighton
University School of Medicine and Catholic Health Initiatives Health
Behavioral Health Services. He is also an adjunct professor of
psychiatry at Yale School of Medicine in New Haven, Connecticut.

References

1. Lee D, Slomkowski M, Hefting N, et al. Brexpiprazole for the

treatment of agitation in Alzheimer dementia: a randomized clinical
trial. JAMA Neurol. 2023:e233810.

2. Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of

reports of randomized clinical trials: is blinding necessary? Control
Clin Trials. 1996;17(1):1-12.

3. Grossberg GT, Kohegyi E, Mergel V, et al. Efficacy and safety of

brexpiprazole for the treatment of agitation in Alzheimer’s dementia:
two 12-week, randomized, double-blind, placebo-controlled trials. Am
J Geriatr Psychiatry. 2020;28(4):383-400.

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