Symptoms With Potential Diagnostic Utility in Bipolar

and Unipolar Depression: A Probabilistic Approach

• Early onset of depression (<25 years)
• Multiple prior episodes (≥5)
• Positive family history of bipolar disorder
• Hypersomnia/increased daytime napping
• Hyperphagia/increased weight
•
Bipolar •
Atypical depression signs
Psychomotor retardation
Depression • Psychotic features/pathological guilt
• Mood lability/irritability/psychomotor agitation/racing thoughts
• Post-partum affective symptoms
• Substance abuse
• Anxiety disorders

• Late onset of first depression (>25 years)

• Long duration of current episode (>6 months)
• Negative family history of bipolar depression
Unipolar • Initial insomnia/reduced sleep
• Appetite/weight loss
Depression • Normal or increased activity levels
• Somatic complaints
• Tendency to blame others
• Anxiety
RM
McIntyre RS, Calabrese JR. Curr Med Res Opin 2019;5:1-13; McIntyre RS et al. Lancet 2020: S0140-6736(20)31544-0.
 Rapid Mood Screener (RMS)
Download for free. DOI: 10.1080/03007995.2020.1860358
Item Response
1. Have there been at least 6 different periods of time (at least 2 weeks) Yes No
when you felt deeply depressed?
2. Did you have problems with depression before the age of 18? Yes No
3. Have you ever had to stop or change your antidepressant because it Yes No
made you highly irritable or hyper?
4. Have you ever had a period of at least 1 week during which you were Yes No
more talkative than normal with thoughts racing in your head?
5. Have you ever had a period of at least 1 week during which you felt any of Yes No
the following: unusually happy; unusually outgoing; or unusually
energetic?
6. Have you ever had a period of at least 1 week during which you needed Yes No
much less sleep than usual?
Highest estimated accuracy was observed with ≥4 “yes” responses
• RMS sensitivity was 0.88 and specificity was 0.80; concordance index 0.87
• MDQ sensitivity was 0.86 and specificity was 0.78; concordance index 0.82

McIntyre RS et al. Curr Med Res Opin 2021;37(1):135-44. RM

 Probabilistic Approach to Diagnosis
 A ‘probabilistic’ approach may help identify patients who are more likely to have bipolar mood disorders

‒ Many factors are more common in BPD than in unipolar depression

‒ The presence of any of these probabilistic factors is not necessarily indicative of mixed states, but accumulation of
these factors should alert clinicians to the possibility of MDD with mixed features

Clinical History
Unipolar Family history of bipolar Treatment History Bipolar
disorder
Early age of onset of first Worse response to Symptoms
depressive episode (<25 years) antidepressants
# of lifetime affective episodes Antidepressant-induced Psychotic features
hypomania Atypical depressive symptoms
# of hospitalizations
Rapid onset of depressive Subsyndromal hypomanic
episodes symptoms
Greater severity of depressive Impulsivity
episodes Aggression
Hostility
Comorbid SUD

McIntyre RS et al. Lancet 2020;396(10265):1841-56. RM

The “Four A’s” Increase Suspicion of Mixed Features

Clinicians should be aware of “the four A’s”:

 Anxiety
 Agitation
 Anger/irritability
 Attentional disturbance-distractibility

These symptoms are highly suggestive of

mixed features in individuals with mood
disorders

McIntyre RS et al. Lancet 2020;396(10265):1841-56. RM

Mixed Features Commonly Encountered in Adults With Both MDD and Bipolar
Disorder: The International Mood Disorders Collaborative Project

% of individuals who met criteria for MFS during an

40
index major depressive episode

35

30 34.0% 33.8%
Percentage (%)

25
26.0%
20

15

10

0
MDD BD-I BD-II
(n=149) (n=65) (n=49
)
*Data from a post hoc analysis of participants who met criteria for a current mood episode as part of MDD (n=506) or BD (BD-I: n=216, BD-II: n=130)

 Mixed features specifier (MFS) was operationalized as a score ≥1 on 3 or more select items on the Young Mania Rating Scale
(YMRS) or ≥1 on 3 select items of the Montgomery-Åsberg Depression Rating Scale (MADRS) or Hamilton Depression Rating Scale
(HAMD-17) during an index major depressive episode (MDE) or hypo/manic episode, respectively

McIntyre RS et al. J Affect Disord 2014;172C:259-64. RM

 Is Antidepressant Resistance a Predictor of Bipolar
Disorder?
30 –
Change in diagnosis from MDD DIFFICULT
DTT
to BP with stratified responses to TO
25 – antidepressants during an 8-year TREAT
Rates of diagnosis change from

follow-up (n = 1,485) INTERMEDIATE

20 – DIFFICULTY TO
MDD to bipolar disorder

TREAT
EASY TO TREAT (no
15 –
meds required)
ITT
10 –
ETT-1
ETT-2
5–
EASY TO TREAT (one
0– med required)
2000 2001 2002 2003 2004 2005 2006 2007
MDD = major
depressive Participants with medication-resistant history (difficult-to-treat group [DTT]) without any antidepressant use (easy-to-treat group 1 [ETT-
1]) or those without any change in antidepressant (easy-to-treat group 2 [ETT-2]). Participants who changed antidepressant just once,
disorder after an adequate antidepressant trial (intermediate level of difficulty to treat [ITT]).

Li CT et al. Br J Psychiatry 2012;200(1):45-51. RM

Interaction of BP Diagnosis and Childhood Maltreatment
Is Associated With Adult Morbidity

^ * *p<0.05

* ref ^p=0.06

* * N=674

The interaction of bipolar diagnosis and childhood The interaction of bipolar diagnosis and number of
maltreatment type is associated with odds of having at childhood maltreatment histories is associated with odds
least one medical illness in adulthood of having at least one medical illness in adulthood in a
dose-dependent manner

Hosang GM et al. Br J Psychiatry 2018;213(5):645-53. RM

 Cardiovascular and Metabolic Comorbidities Are Prevalent
Among Patients With Bipolar Disorder
Comorbid CVD contributes to greater mortality than does suicide in patients with bipolar disorder.1,7

 Endocrine and metabolic disorders and high BMI may be

associated with poorer recovery from depressive episodes4,7
Up to 54% of
 Metabolic risk factor monitoring should be incorporated into patients with
patient management plans5,6 bipolar
disorder have
 Medications for bipolar depression are associated with metabolic
metabolic abnormalities to varying degrees—an important syndrome.2
factor when weighing limited treatment options5,6

BMI, body mass index; CVD, cardiovascular disease; HDL-C, high-density lipoprotein cholesterol; TG, triglycerides.
1. Weiner M et al. Ann Clin Psychiatry 2011;23(1):40-7.
2. de Almeida KM et al. CNS Neurosci Ther 2012;18(2):160-6.
3. International Diabetes Federation. The IDF Consensus Worldwide Definition of the Metabolic Syndrome. Brussels, Belgium: IDF Communications;
2006.
4. Kemp DE et al. Bipolar Disord 2010;12(4):404-13.
5. Cooper SJ et al. J Psychopharmacol 2016;30(8):717-48. doi: 10.1177/0269881116645254. Epub 2016.
6. ADA, APA, AACE, NAASO. Diabetes Care 2004;27(2):596-601.
7. Liu YK et al. J Affect Disord 2021;S0165-0327(21)01427-0.
RM
 Prevalence of Type 2 Diabetes Mellitus, Impaired Fasting Glucose, General
Obesity, and Abdominal Obesity in Patients With Bipolar Disorder: A Systematic
Review and Meta-Analysis
Relative risk of developing type 2 diabetes mellitus in bipolar patients and age- and gender-matched non-bipolar
populations

Liu YK et al. J Affect Disord 2021;S0165-0327(21)01427-0. RM

 Obesity May Predict Bipolarity in
Depressed Patients
20
(hypo)manic symptoms
15
Mean # of lifetime

10

0
Non-obese BMI  30 BMI  35

Vannucchi et al. J Affect Disord 2014;156:118-22.

RM
Obesity in Patients With Major Depressive Episode (MDE)
Is Related to Bipolar and Mixed State Diagnostic Criteria

MDE-Obese (n=493) > MDE-Not Obese (n=2,291)

DSM-IV Bipolar • DSM-IV Bipolar I 

Disorder • DSM-IV Bipolar II X

• Bipolar I specifier 
Bipolar Specifier
• Bipolar II specifier X

Depressive Mixed • DSM-5 criteria  RBDC=Research-

State • RBDC mixed depression  Based Diagnostic
Criteria

Petri E et al. Bipolar Disord 2017;19(6):458-64. RM

 Prevalence of Type 2 Diabetes Mellitus, Impaired Fasting Glucose, General
Obesity, and Abdominal Obesity in Patients With Bipolar Disorder: A Systematic
Review and Meta-Analysis
Relative risk of developing general obesity in bipolar patients and age- and gender-matched non-bipolar populations

Liu YK et al. J Affect Disord 2021;S0165-0327(21)01427-0. RM

 Functional Recovery in Bipolar Disorder
Percentage of Patients With First-Episode Psychotic Affective Disorders Who Reached Syndromal
(N=199) and Functional (N=181) Recovery Within 6 and 24 Months After First Lifetime Hospitalization

Tohen M et al. Am J Psychiatry 2000;157(2):220-8. RM

 Treatments Reported to Be Efficacious
Across the Various Phases of Bipolar Disorder
ACUTE BIPOLAR DEPRESSION ACUTE MANIA MAINTENANCE

Treatments APPROVED All treatments APPROVED All treatments APPROVED

by the FDA by the FDA, except for* by the FDA, except for*
 Cariprazine  Lithium  Lithium
 Lurasidone  Divalproex  Aripiprazole (oral and
 Quetiapine  Carbamazepine long-acting injectable)
 Olanzapine-fluoxetine  Aripiprazole  Asenapine
 Lumateperone  Asenapine  Lamotrigine
 Cariprazine  Paliperidone*
 Chlorpromazine  Quetiapine
Treatments not approved  Haloperidol* (adjunctive)
 Olanzapine  Olanzapine
by the FDA
 Paliperidone*  Risperidone (long-
 Lithium
 Quetiapine acting injectable)
 Lamotrigine
  Risperidone
Antidepressants
  Ziprasidone
Electroconvulsive therapy
 Combination treatment with either
 Repetitive transcranial
aripiprazole, asenapine, olanzapine,
magnetic stimulation
quetiapine, or risperidone and
lithium or divalproex

Adapted from McIntyre RS. Lancet 2020;396(10256):1841-56. AC

 Complex Polypharmacy in Bipolar Disorder
Is the Rule Rather Than the Exception
Representative Percentages of Patients With Bipolar Disorder Receiving
3 or >4 Psychotropic Medications During Postacute Maintenance Treatment Across Major Studies

3 Medications

≥4 Medications

0 5 15 20 30 40 45 50
25 35 AMSP
10 Swedish National Registry EMBLEM Stanley-Pittsburgh
Bipolar Choice STEP-BD Institute of Living
AMSP, Institut fur Arzneimittelsicherheit in der Psychiatrie.
Freedom From Fear Butler
Kim AM et al. J Clin Psychiatry 2021;82(3):20r13263. AC
 Second-Generation Antipsychotic
Drugs in Bipolar Depression
Adjunctive
Monotherapy (to Lithium or Valproate)

Bipolar I Bipolar II Bipolar I Bipolar II

Lumateperone*   

Quetiapine1

Olanzapine/fluoxetine2 

Lurasidone3  

Cariprazine4 
*Lumateperone has FDA approval for the treatment of schizophrenia in adults. Safety and efficacy have not been established for other uses.

1. Quetiapine fumarate PI. 2. Olanzapine and fluoxetine PI. 3. Lurasidone hydrochloride PI. 4. Cariprazine PI.
AC
Olanzapine-Fluoxetine Combination (OFC) in Bipolar Depression

Data from two 8-week randomized clinical trials for bipolar depression. Primary measure was
change in MADRS; OFC was significantly superior to both OLZ and PBO.
OFC: n=86, mean daily dose 7.4 mg/39.3 mg. OLZ: n=370, mean daily dose 9.7 mg. PBO:
n=377.
AC
 Acute Responder Efficacy of Lurasidone
in Bipolar Disorder I Depression
Adjunctive Design1 Monotherapy Design2 Mean baseline doses
100 100 of lithium in the
lurasidone and placebo
80 80 groups: 897.2 mg/day
and 947.3 mg/day,
† † respectively
Patients (%)

57
60 60 53 51
42 Mean baseline doses
40 40 of valproate in the
30
lurasidone and placebo
20 20 groups: 1058.3 mg/day
and 1117.8 mg/day,
respectively
0 0
Placebo + Li/VPA Lurasidone + Li/VPA Placebo Lurasidone Lurasidone
(N = 161) (N = 179) *P <.01 (N = 162) 20-60 mg 80-120 mg
NNT = 7 †P <.001 (N = 161) (N = 162) Li, lithium; LOCF, last observation
NNT = 5 NNT = 5 carried forward; MADRS,
Responder criteria: ≥50% reduction from baseline in MADRS at LOCF endpoint. Montgomery-Asberg Depression
Rating Scale; NNT, number needed
NNT: 1/( % responders on active compound - % responders on placebo) to treat; VPA, valproate.

1. Loebel A et al. Am J Psychiatry 2014;171(2):169-77. 2. Loebel A et al. Am J Psychiatry 2014;171(2):160-8. AC

 Bipolar Depression With Mixed Features: Lurasidone

Change From Baseline in MADRS Score (MMRM):

Patients With and Without Mixed Features at Baseline (mITT Population)
Baseline Wk 1 Wk 2 Wk 3 Wk 4 Wk 5 Wk 6
0 Lurasidone effective in
improving depressive
LS Mean Change in MADRS Score

-2 *P ˂.05. †P ˂.01. ‡P ˂.001.

-4 symptoms both with
-6 * and without mixed
-8 features
* *
-10 LS, least squares; MADRS,

-12 * Montgomery-Asberg Depression

* Rating Scale; mITT, modified intention-
to-treat; MMRM, mixed model for
-14 * repeated measures.
‡ †
-16 ‡
†
-18 With mixed features lurasidone (n = 182) With mixed features placebo (n = 90)
Without mixed features lurasidone (n = 141) Without mixed features placebo (n = 72)
McIntyre RS. J Clin Psychiatry 2015;76(4):398-405. AC
 Lurasidone Effective in MDD With Mixed Features
LS Mean Change From Baseline

Effect size = 0.80

-13.0

-20.5

Baseline mean = 33.3 33.2

*P <.05. †P <.01. ‡P <.001. MADRS range: 0–60. Mean daily dose of lurasidone: 36.2 mg/day. Mixed model for repeated measures, ITT population.
ITT, intention-to-treat; LS, least squares; MADRS, Montgomery-Asberg Depression Rating Scale; MDD, major depressive disorder.

Suppes T et al. Am J Psychiatry 2016;173(4):400-7. AC

 Cariprazine in Bipolar Depression
With or Without Manic Symptoms
Pooled Analysis of 3 Randomized Trials
Patients With Manic Symptoms Patients Without Manic Symptoms
Baseline Wk 2 Wk 4 Wk 6 Baseline Wk 2 Wk 4 Wk 6
0 0

LS Mean Change From Baseline

LS Mean Change From Baseline

-2 -2
-4 -4
-6 -6
*
-8 -8 †
*
-10 -10 ‡
‡ †
-12 * -12

-14 † -14 ‡
‡
-16 Placebo ‡ -16 Placebo ‡
Cariprazine 1.5 mg/day Cariprazine 1.5 mg/day
*P <.05
Cariprazine 3 mg/day †P <.01 Cariprazine 3 mg/day
‡P ≤.001

McIntyre RS et al. CNS Spectr 2020;25(4):502-10. AC

20-Year Trends in the Pharmacologic Treatment of Bipolar Disorder by
Psychiatrists in Outpatient Care Settings

Trends in Types of Agents Prescribed Trends in Outpatient Prescriptions

1997 to 2000 2013 to 2016
Prescription
Frequency Frequency

Number of Outpatient Visits During

467,000 1,060,000
the Period
Antidepressant 47.0% of visits 57.5% of visits
Antidepressant Without Mood
17.9% of visits 40.9% of visits
Stabilizer

Mood Stabilizers (Including

Carbamazepine, Lamotrigine & 62.3% of visits 26.4% of visits
Valproate)

Lithium 30.4% of visits 17.6% of visits

Second-Generation Antipsychotics 12.4% of visits 51.4% of visits

Rhee TG et al. Am J Psychiatry 2020;177(8):706-15. AC

 Assessing Individual Patient Candidacy for
Antidepressant Use in Bipolar Disorder
Favors Antidepressant Use
BPII
Pure depressed episodes
Absence of rapid cycling
Absence of recent mania/hypomania
Absence of comorbid alcohol/substance use disorders
Prior favorable antidepressant response
No history of antidepressant-induced mania
SLC6A4 l/l genotype
Discourages Antidepressant Use
BPI
Mixed features
Past year rapid cycling
Mania/hypomania in past 2–3 mo
Alcohol or substance use comorbidity
Suboptimal responses to prior antidepressants
History of antidepressant-induced mania/hypomania
SLC64 s/s genotype

BPI, bipolar disorder I; BPII, bipolar disorder II.

Goldberg JF, Stahl SM. Practical psychopharmacology; 2021. AC

 Ketamine Improves Anxiety, Agitation, and Irritability
in Adults With Treatment-Resistant Bipolar Depression
GAD-7 Anxiousness Score GAD-7 Anxiousness

Mean Irritability Score

Mean Anxiety Score
Score

AIA
Non-AIA
Mean Agitation Score

GAD-7 Agitation Score (Trouble Relaxing) GAD-7 Agitation Score (Restlessness)

Mean Agitation Score

AIA, anxiety, irritability and agitation;
GAD-7, Generalized Anxiety Disorder-7 scale. McIntyre RS et al. Bipolar Disord 2020;22(8):831-40. AC
Transcranial Direct Current Stimulation for Bipolar
Depression
N=59 BP I or II depressed Change in Depression Scores Over Time
outpatients on stable med 25
regimens
20
Ten daily 30-minute, 2mA,

HDRS-17 Score
anodal-left cathodal-right Sham tDCS
prefrontal sessions on 15
weekdays, then 1 session every
fortnight until Week 6 10
Active tDCS

5
Baseline Week 2 Week4 Week 6
Time
Response: 67.6% (vs. 30.4% sham); NNT=2.69

Sampaio-Junior et al. JAMA Psychiatry 2018;75:158-66. AC

Misdiagnoses and Underdiagnoses Are Common Among
Patients With Bipolar Disorder

Up to 60% of
depressed
patients with BPII
are initially
diagnosed with
unipolar
depression

Bipolar Depression Unipolar Depression

Stahl SM. Stahl's Essential Psychopharmacology, 5th ed; 2021; Hirschfeld RM et al. J Clin
Psychiatry 2003;64(2):161-74; Singh MK et al. Bipolar Disord 2021;23(8):834-7.
Factors That Contribute to Misdiagnosis

Reasons for misdiagnosis:

► Incomplete understanding of bipolar disorder
by healthcare professionals
► Overlooked or no history of mania
Misdiagnosis ► Failure to differentiate symptoms that can help
identify unipolar and bipolar depression

Bipolar Consequences of misdiagnosis:

Depression ► Inappropriate use of antidepressant agents
► Increased acute risk of switching from depression
to mania/hypomania with antidepressant use
► Delay of proper treatment

McIntyre RS et al. Curr Med Res Opin 2019;35(11):1993-2005.

Why Is an Early, Accurate Diagnosis Important?

Consequences of not identifying bipolar depression (BD) early:

Impaired quality of life

Inaccurate and potentially harmful treatment

Increased cycling and risk of relapse

Increased risk of suicide

Increased subsequent morbidity

High economic costs

Overall mortality rate for BP is

over 2.5X higher than the
general population

Conus P et al. Bipolar Disord 2014;16(5):548-56; Lomholt LH et al. Int J Bipolar

Disord 2019;7(1):6; Youngstrom EA at al. 2008;10(1 Pt 2):194-214.
 Barbara Geller’s Work in Pediatric Bipolar
Disorder and 25-year Follow-Up
Barbara Geller's work on pediatric BD: strong association
with early-onset depression, with family history, and that
grandiosity and hypersexuality are common mania
symptoms and can help differentiate from ADHD, as well
as the common presentation of mixed states as manic
equivalents.
7
3
relapse
In the 25-year preliminary analyses participants with %
baseline BD: after
- remained more impaired as rated by trained observers o
recovery
f
- had higher rates of mania, depression, and substance
use in adulthood
- those who had mania in adulthood had higher rates of
many “cardinal symptoms” at baseline
- those who continued to have mania in adulthood had
more severe decreased need for sleep, grandiosity, and Geller et al., Arch Gen Psych 2008
hypersexuality than those that did not.
Alecia Vogel-Hammen, In Preparation
 Serotonin/Dopamine Antagonists/Partial Agonists
Across the Depression Spectrum

• There is a major paradigm shift away from monoamine reuptake

inhibitors for depression with mixed features
• Serotonin/ dopamine antagonists/ partial agonists are
effective at treating: bipolar depression and treatment-resistant
depression (TRD)

• Several of the agents that are approved for bipolar depression are also
effective for depression with mixed features

• There are currently no agents approved to treat mixed depression

Stahl SM. Stahl's Essential Psychopharmacology, 5th ed; 2021.

 Atypical Antipsychotics

DMX: depressive mixed state;

MMX: mania with mixed features Stahl SM. Stahl's Essential Psychopharmacology, 5th ed; 2021.
FDA-Approved Treatments for Pediatric Bipolar Disorder
Acute Mania Acute Bipolar Depression Longer-Term

Year/ Drug Year/ Drug Year/ Drug

1970 Lithium (Age ≥ 12–17) 1 Lithuim (Age ≥

2007 Risperidone (Age 10–17)

2008 Aripiprazole (Age 10–17) e)

Unmet
Unmet
Need
2009 Quetiapine (Age 10–17)

2009 Olanzapine (Age 13–17) Need

2015 Asenapine (Age 10–17)

*Adjunctive (as well as monotherapy);

Important unmet needs—well-tolerated treatments for acute depression
and maintenance
(->e)Extrapolated indication
Adapted from Ketter TA (ed). Advances in the treatment of bipolar disorder, Am Psych Pub, Inc., Washington,
DC; 2015; Roley-Roberts ME, Fristad MA. J Clin Child Adolesc Psychol 2021;50(4):464-77.
Risk Factors for Developing Arousal Induced by Medication
(AIM)
Premorbid
Psychiatric
Symptoms
Drug Factors (e.g., mania,
ADHD, anxiety)
Demographic
(dose, time/pace of dosing, Factors
bioavailability,
(age, sex)
metabolism,
drug-drug interactions)

RISK FOR
AIM?
Genetics
Neural Factors (CYP P450
(amygdala volume, polymorphisms)
prefrontal-limbic
connectivity,
physiology) Family History

A Double-Blind Randomized Trial to Investigate Mechanisms of Antidepressant-Related Dysfunctional Arousal in Depressed or

Anxious Youth at Familial Risk for Bipolar Disorder. Honeycutt DC, DelBello MP, Strawn JR, Ramsey LB, Patino LR, Hinman K,
Welge J, Miklowitz DJ, Jo B, Blom TJ, Bruns KM, Hamill Skoch SK, Starace N, Tallman MJ, Singh MK. J Pers Med 2022;12(6):1006.
Lurasidone in Pediatrics With Mixed Features
Youth with Bipolar I Depression have similar
efficacy/safety profiles with/without subsyndromal
hypomania

Singh et al. Journal of Child and Adolescent Psychiatry 2020;30(10):590-8.

Sleep Disturbance, Irritability, and Response to Lurasidone Treatment in Children and Adolescents With Bipolar Depression

BACKGROUND QUESTION
-Mixed features in youth with bipolar Depressive Mania Do bridge symptoms moderate the acute
depression affect treatment outcomes Symptoms Symptoms
and long-term treatment effects of
-Bridge symptoms overlapping between lurasidone in youth with bipolar
depressive and manic states may depression?
moderate treatment effects Reduced Sleep Irritability Decreased Need for Sleep

Acute Treatment Results Long-Term Treatment Results

CONCLUSIONS: Successful remediation of sleep disturbance and irritability improved the effect of lurasidone on
depressive symptoms; targeting bridge symptoms like sleep disturbances may ameliorate treatment outcomes.
Singh MK et al. Curr Neuropharmacol 2022;doi: 10.2174. Online ahead of print.
Patient Centricity to Optimize Clinical Outcomes

What do our patients Barriers to meeting these needs with current

want/need? treatments:
- Hard to achieve symptom control AND self-care,
social, educational, work functioning.
- Residual and comorbid symptoms interfere with
- Symptom relief function.
- Recovery - Medication side effects lead to more symptoms and
- Satisfactory quality of life nonadherence.
- Treatments target only part of the disorder.
- Adequate functioning Comprehensive care (integrating medication
management and psychotherapy) to optimize
treatment engagement is elusive.

Correll CU. Using patient-centered assessment in schizophrenia care: defining recovery and discussing concerns and preferences,
J Clin Psychiatry 2020 Apr 14;81(3):MS19053BR2C.
Lauriello J. Patient-centered psychopharmacology and psychosocial interventions: treatment selection and shared decision-making to
enhance chances for recovery, J Clin Psychiatry 2020 May 12;81(3):MS19053BR4C.