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A manic episode is a psychiatric condition characterized by the presence of elevated, expansive, or irritable mood; grandiosity; increased goal-directed activity; risk-taking behaviors; pressured speech; decreased need for sleep; racing thoughts; and distractibility. Most commonly, manic episodes occur because of an underlying primary bipolar disorder. However, manic episodes can occur as a result of multiple other causes, including general medical conditions, substance abuse, and medication side effects. One medication that has been hypothesized to precipitate manic episodes is the chemotherapy agent methotrexate.

Methotrexate is used in the treatment of multiple forms of 

 through folate antagonism; it is also used to treat multiple autoimmune conditions.

 Although there is very limited literature describing an association between methotrexate and the occurrence of manic episodes, there have been reported cases of manic episodes in patients with stable bipolar disorder following the administration of methotrexate.

 To date, however, there have been no reported cases of manic episodes precipitated by methotrexate in patients without an existing diagnosis of bipolar disorder.

This case report demonstrates the acute onset of mania in a patient with no history of 

, which putatively was precipitated by the use of intrathecal methotrexate in the treatment of acute lymphoblastic leukemia.

“Charlie” is an adolescent patient with a prior psychiatric history of attention-deficit/hyperactivity disorder (ADHD) and a medical history of acute lymphocytic leukemia (ALL). He had no prior history of affective or psychotic disorders. Family history was significant for depression in a maternal aunt, but there was no family history of bipolar disorder or psychosis. After the patient was diagnosed with high-risk ALL, he was started on induction chemotherapy. He completed a course of prednisone treatment and received a second dose of intrathecal methotrexate (IT MTX) a few days prior to presentation.

At that time, Charlie presented to the hospital with several days history of altered mental status in the form of irritability, elevated mood, poor sleep, pressured speech, grandiosity, 

Upon admission, computed tomography (CT) head without contrast, magnetic resonance imaging (MRI) brain with and without contrast, magnetic resonance angiography (MRA) head without contrast, and magnetic resonance venography (MRV) head with and without contrast were all unremarkable. Awake electroencephalogram (EEG) was normal. Labs including anti- hyroperoxidase (TPO), thyroid peroxidase antibody, paraneoplastic antibody panel, autoimmune encephalopathy panel, and N-methyl-D-aspartate (NMDA) receptor antibody (CSF and serum) were negative. Ammonia, ceruloplasmin, Vitamin B12, TSH, and T4 were normal.

After being evaluated by the psychiatric consult liaison (C-L) team, Charlie was started on olanzapine, which was titrated to 10 mg BID for treatment of acute manic and psychotic symptoms. During the following days, Charlie remained disorganized and delusional, so olanzapine was changed to haloperidol 1 mg BID. The next few days he was reported to be doing marginally better, with improved 

 and less pressured speech, though remained somewhat disorganized and delusional.

On day 9 of admission, Charlie received third IT MTX treatment. On the following day, he was very restless, making bizarre hand movements, pacing around the room, with pressured speech and tangential thoughts, and remained hyper-religious with delusions of grandeur. Following reassessment by the C-L team, he was started on sodium valproate and quetiapine in addition to haloperidol 1 mg BID. Total daily doses of sodium valproate and quetiapine were gradually titrated up to 1250 mg and 350 mg, respectively. Charlie could not tolerate further increases in quetiapine beyond 350 mg daily due to excessive sedation, and haloperidol was discontinued due to prolonged QTc. Lorazepam 1 mg TID was added for management of agitation and irritability.

During the following days, Charlie’s sleep started to improve with periods of lucid thoughts. He gradually became much calmer and redirectable, although remained occasionally delusional. As his mental status started to improve, quetiapine was decreased to 300 mg daily and lorazepam was decreased to 0.5 mg in the evening. Sodium valproate was continued at 1250 mg daily.

On day 16, Charlie received a fourth scheduled IT MTX treatment, with deterioration of mental status by the following day. He was noted to have more disorganized speech and delusional thoughts. Quetiapine was gradually titrated to 700 mg daily while sodium valproate was kept at 1250 mg daily.

Charlie showed marked improvement in mental status over the next few days of treatment, with less pressured speech and less disorganization. He continued to have tangential and racing thoughts but with much less intensity. Following stabilization, Charlie was discharged to home on a medication regimen that consisted of sodium valproate 1250 mg daily, quetiapine 700 mg daily, and lorazepam 0.5 mg TID.

After discharge, Charlie was followed by the psychiatric C-L team during outpatient visits to the Hem/Onc clinic. Five days after discharge, his thought process and behavior were noted to be much more organized. He continued to have some delusional thinking but was able to interact and engage in daily activities. Due to complaints of tiredness and increased sleep during the daytime, quetiapine was decreased to 500 mg daily and lorazepam was discontinued. Sodium valproate was continued at 1250 mg daily.

Twelve days following discharge, Charlie received fifth and last IT MTX treatment as scheduled. Six days after that, he was readmitted with acute manic and psychotic symptoms similar to the first admission. Following evaluation by psychiatry, Charlie was continued on sodium valproate 1250 mg daily, and quetiapine was increased to 600 mg daily. Due to elevated valproic acid (113.4 ug/mL, ref range 50-100 mcg/mL) and ammonia (97 umol/ L, ref range 11-32 umol/ L) levels, sodium valproate was subsequently decreased to 750 mg daily. During the following days, his behavior and mental status started to improve. After 6 days of hospitalization, the patient was discharged home on quetiapine 600 mg daily and sodium valproate 750 mg daily.

Seven days later, the patient presented at the outpatient clinic with markedly improved mental status and overall functioning. Sodium valproate 750 mg daily and quetiapine 500 mg daily were continued.

Given that Charlie presented with 4 episodes of severe manic symptoms with psychotic features after administration of intrathecal MTX, a causal association was assumed between the intrathecal MTX and development of these symptoms. After significant discussions between psychiatry and hem/onc, the decision was made to switch ALL treatment from IT MTX to intrathecal cytarabine/hydrocortisone (IT ARAC/HCZ) with oral MTX.

As a result, Charlie continued to present psychiatrically stable with no acute affective or 

. Psychotropic medications were gradually tapered off until they were discontinued 3 months after discharge. As per chart review, he remained psychiatrically stable over the next 2 years.

It is worth noting that Charlie received steroids in addition to IT MTX before the onset of first manic episode. No steroids, however, were given in combination with IT MTX prior to subsequent episodes. When treatment was switched to intrathecal steroid (IT ARAC/HCZ) with oral methotrexate, he remained psychiatrically stable with no further manic episodes reported.

In children with acute lymphoblastic leukemia, the addition of methotrexate to treatment protocols has been found to be beneficial in preventing central nervous system relapse.

 Methotrexate is a folate antagonist that is used for treating a variety of medical conditions including psoriasis, rheumatoid arthritis, and other 

Methotrexate inhibits dihydrofolate reductase (DHFR), the enzyme that reduces folic acid to tetrahydrofolic acid.

 The inhibition of DHFR by folate antagonists (methotrexate) results in a deficiency in the cellular pools of thymidylate and purines, and thus a decrease in nucleic acid synthesis. Therefore, methotrexate interferes with DNA synthesis, repair, and cellular replication. It also markedly interferes with transmethylation reactions, which are crucial for the formation of proteins, lipids, and also myelin, presumably leading to demyelination of nervous tissues.

Few mechanisms of precipitation of manic symptoms by methotrexate have been hypothesized. One possible cause is the interference of folate metabolism, as folic acid is used in the body to manufacture serotonin and dopamine neurotransmitters. Other postulations include interference in glutaminergic neurotransmission (increased release in glutamate and aspartate) by high levels of homocysteine and sulfur-containing amino acids, which is caused by the interference in folate metabolism.

 Glutaminergic neurotransmission is implicated in the pathophysiology of bipolar affective disorder and some studies report patients with manic episodes show elevated glutamate and glutamine.

Cytotoxic agents including methotrexate are potent neurotoxins. Although neurotoxicity has been observed with high dose oral or intrathecal methotrexate, to date there have been no published reports in the literature in which methotrexate precipitated a 

 in a patient with no prior history of bipolar disorder.

There are multiple drugs that are implicated in the development of manic symptoms, including antidepressants, steroids, levodopa, amphetamine, and phencyclidine, but methotrexate is not commonly implicated.

 In Charlie’s case, the contingency of the symptoms on methotrexate use and improvement on withdrawal of the drug and treatment of the manic episode suggest a causal relationship. 

ADHD has been genetically linked to bipolar disorder,

 and that may offer an explanation, at least in theory, about why this particular patient was more vulnerable to developing manic episodes.

In cases where mania is thought to be precipitated by IT MTX, we would recommend using an alternative medication or route of administration in addition to the use of psychotropic medications to manage the acute manic symptoms as appropriate.

To our knowledge, this is the first case report of acute onset mania in a patient with no prior personal or family history of bipolar disorder during IT MTX. It adds to the limited literature of methotrexate-induced mania in patients with previously stable bipolar disorder. Collectively, these reports contribute to the poorly understood relationship between bipolar disorder and treatment with cytotoxic agents, such as methotrexate.

is a child and adolescent psychiatrist, as well as an adjunct clinical assistant professor of psychiatry at Indiana University School of Medicine.

is an assistant professor at Emory University School of Medicine and is the Program Director for Emory’s Child and Adolescent Psychiatry Fellowship Program.

is the medical director for the psychiatry consultation-liaison service for Children’s Healthcare of Atlanta and adjunct assistant professor at Emory University School of Medicine.

is an assistant professor at Emory University School of Medicine.

1. Bedford Laboratories. Methotrexate for injection prescribing information. 2012. 

https://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Ben%20Venue_Bedford%20Labs/55390-031-10%20MTX%2050MG/5539003110

2. Hariram J, Jegan Y. Contribution of methotrexate in precipitation of manic episode in bipolar affective disorder explored: a case report. 

3. Bührer C, Henze G, Hofmann J, et al. Central nervous system relapse prevention in 1165 standard-risk children with acute lymphoblastic leukemia in five BFM trials. 

4. Raimondi MV, Randazzo O, La Franca M, et al. DHFR inhibitors: reading the past for discovering novel anticancer agents. 

5. Vezmar S, Becker A, Bode U, Jaehde U. Biochemical and clinical aspects of methotrexate neurotoxicity. 

6. Sanacora G, Rothman DL, Mason G, Krystal JH. Clinical studies implementing glutamate neurotransmission in mood disorders. 

7. Michael N, Erfurth A, Ohrmann P, et al. Acute mania is accompanied by elevated glutamate/glutamine levels within the left dorsolateral prefrontal cortex. 

8. Ongür D, Jensen JE, Prescot AP, et al. Abnormal glutamatergic neurotransmission and neuronal-glial interactions in acute mania. 

9. Gigante AD, Bond DJ, Lafer B, et al. Brain glutamate levels measured by magnetic resonance spectroscopy in patients with bipolar disorder: a meta-analysis. 

10. Preda A, Shapiro B, Bienenfeld D. Substance-induced mood disorder. 

https://emedicine.medscape.com/article/286885-overview

11. Osser DN. ADHD in patients with bipolar disorder: genetics, diagnosis, and treatment. 

https://www.psychiatrictimes.com/view/adhd-bipolar-genetics-diagnosis-treatment

A case report and literature review of intrathecal methotrexate-induced mania.

 Can This Cancer Treatment Cause Manic Episodes?

When the email from “Sam” arrived asking about adding a natural weight loss product to his more mainstream prescription medications, I was not surprised. Binge eating was his bête noire. A onetime college athlete who lost his scholarship because of an ankle injury, he had since sat around eating while watching sports on TV and lamenting his lost career. He desperately wanted to shed unwanted weight, but treatments that control bingeing do not guarantee weight loss. He had tried 

 with no success. So, when he heard about a new natural weight loss concoction, he was understandably excited yet skeptical because he knew of the government’s crackdown on hoodia.

Sam forwarded me a laundry list of ingredients without hoodia but with 

 (Pausinystalia yohimbe). Years had passed since I had seen that word in print.

“Was it safe?” was all he wanted to know. Whether it worked seemed to be a secondary concern. My short answer was no, and I promised a longer explanation at his next appointment. In the interim, flashbacks of another patient from long ago popped up. Although psychopharmacology has quickly evolved in the decades since the 

, that related case was too dramatic to forget.

I remember the frantic call from the ED staff, begging me to see their patient posthaste.

“Maybe you can prescribe lithium or haloperidol or something like that. We cannot contain him here, but we have nowhere to send him,” said the pressured voice on the phone. “He saw a psychiatrist, but that is all we know.”

It was Sunday midmorning, late summer, when many Manhattanites escape town leaving side streets empty and opening tables at New York City’s unending array of eateries. Uninterrupted by impatient New Yorkers demanding seats, out-of-towners could enjoy unhurried brunches, fussed over by glamorous waitstaff who were patiently anticipating their Broadway debuts. The tidy townhouses lined side by side behind the hospital conveyed an extra sense of calm that contrasted with rowdy Saturday nights.

 which was nearly abandoned. I peered through the window of the make-do quiet room and could see that the doctor who called the consult was not exaggerating. A tanned, middle-aged man stood a few feet behind the door. He looked to be 50-something, but he jumped and hopped like a child, in sync to the beat of an invisible drum. His thinning silver hair swung wildly. Most strikingly, his suit jacket was draped around his waist, hiding his backside and little else. Empty sleeves looped across the front, dangling like a loincloth, albeit one with a shiny—probably pricey—silk lining. Where he left his pants, shoes, socks, and shirt was anyone’s guess. All I knew is that he wore nothing else.

Per protocol, I checked the chart before walking into the room, not just for safety’s sake but to

 by skimming the demographics. He was, in fact, middle-aged, married, and, in hindsight, possibly a vestige of the 

 had not aired yet. For that matter, sildenafil had not been invented, nor had the now-ubiquitous second-generation antipsychotics that are often used to treat bipolar disorder. Per the intake sheet, “Mr Smith” was a senior vice president at a name-brand advertising firm, even if his present posture suggested otherwise.

The history mentioned that his private psychiatrist, who had retreated to the Hamptons for the summer, referred all emergencies to the hospital, as per his answering machine message. Before leaving, said psychiatrist started him on lithium, then carbamazepine, maybe even 

, but now everything spiraled out of control. Experience told me that advertising executives with bipolar disorder tendencies are not uncommon, because advertising takes high energy, unabashed enthusiasm, and lots of chutzpah, which are abundant in 

. Yet it was also unlikely that someone with uncontrolled bipolar disorder could rise so high through the corporate ranks, even if his prescriptions screamed bipolar. It was also unlikely that this behavior represented garden-variety bipolar disorder, because the nurse noted that he was disoriented to time and place, distracted, and responding to unseen stimuli. His rapid, jerky movements put me on high alert for impending seizures, even though a cursory 

I scrolled through the medication list, checked the charted vital signs, scanned all labs listed, and looked for clues to explain this seemingly sudden deterioration. Even the toxicology screens were negative. The medications included several antihypertensives, which opened the possibility of a recent cerebrovascular accident secondary to hypertension, but he was moving all 4 limbs without restrictions, and his frenetic, dancelike activity functioned as a makeshift 

 stress test, making it unlikely (but not impossible) that his strange symptoms followed hypoperfusion. There was only 1 odd entry, a little, nearly illegible word: Yocon.

In those days, we checked prescription pharmaceuticals through big, bulky Physicians’ Desk Reference editions with thin pages and small print. And that was where I found the culprit: that little word was the trade name for 

, a reputed (but disputed) aphrodisiac used in fertility rituals in Cameroon, Central Africa, according to a memorable medical school ethnopharmacology lecture. I called the man’s internist, who had hospital privileges and even made rounds on weekends. The internist checked his chart and confirmed that a urologist had started the man on prescription yohimbine a few weeks earlier. The doctor noted that he added more antihypertensive medications soon after, which made sense, given that this herb can increase blood pressure and interfere with the efficacy of blood pressure medications.

The nurses crowded outside the room, eager for an explanation, and appreciative of the colorful story behind this mystery. Yohimbine was an α1-adrenergic agonist, a product of an East African tree with a similar name. It was marketed as an 

 and subsequently approved for this purpose, despite equivocal evidence. Whether yohimbine helped in this regard was unclear, but its psychoactive properties were apparent. I wondered whether prescriptive yohimbine (or nonmedicinal yohimbe bark) directly increased libido as advertised, or whether it simply induced 

 in susceptible individuals, with the attendant hypersexuality of mania.

That theory was within the realm of possibility, especially because recent reports confirm that the stimulant especially affects individuals who are predisposed to bipolar disorder, as well as schizophrenia, panic disorder, and 

. Even popular online consumer medical websites warn against its use in cases of depression because it can precipitate manic reactions.

 The National Institute of Health’s National Center for Complementary and Alternative Medicine, now the National Center for Complementary and Integrative Health, has since taken a 

, warning against its use in individuals with any psychiatric history.

Over time, we learned much about yohimbine and its positive and negative effects. Although it fell into disuse after the invention of the much more predictable 

 indicated for erectile dysfunction, online marketers still promote it for a wide range of problems, including appetite suppression and obesity. Yohimbine gained greatest use as a veterinary antidote to animal tranquilizers. It has been misused by some humans, as was the case with ketamine, a onetime animal tranquilizer turned club drug that has recently been repurposed as a treatment for depression. No comparable success stories have been reported for yohimbine, although bodybuilders cite anecdotal evidence that the herb enhances exercise endurance. In contrast, forensic medicine journals 

 and note that yohimbine can cause delirium, hallucinosis, seizures, and sometimes deaths. An 

article in American Journal of Psychiatry

confirms that it can switch depression into mania.

Importantly, dangerous interactions can occur with 

—so it was fortunate that the patient quieted down with a dark, soundless room and intravenous diazepam, prescribed by the neurologist to stop seizures should they occur. Aided by the tincture of time, and a short stay upstairs once a bed opened, he reportedly returned to baseline. When I checked on him a few days later, he did not recall this episode.

In hindsight, our mystery man escaped easily. Who knows what tragedies could have occurred had strong psychotropics been added to his medication mix without stopping the clandestine culprit? At worst, lethal medication interactions could have followed. And, at best, he would have been condemned to a lifetime’s treatment for a condition that might not have emerged without this botanical boost.

, and we must consider the big picture, without reflexive and thoughtless prescriptions for psychotropics—even if the general public, as well as other medical professionals, assume that is all we do. As for Sam, I expect him to appreciate this warning story about yohimbine, even if the negative studies about its efficacy for weight loss disappoint him.

is assistant clinical professor of psychiatry and behavioral sciences at Icahn School of Medicine at Mount Sinai, New York, NY.

Three cases of manic symptoms following yohimbine administration

2. Yohimbe. National Center for Complementary and Integrative Health. Updated November 2020. Accessed December 21, 2020. 

3. Anderson C, Anderson D, Harre N, Wade N. 

Case study: two fatal case reports of acute yohimbine intoxication.

As physicians first, psychiatrists must consider the big picture, without reflexive and thoughtless prescriptions for psychotropics—even if many, including medical professionals, assume that is all we do.

Never Forget the Fine Print: From Fertility Rites to “Miracle Med”

Delusional disorder is a major psychotic illness that is enigmatic and poorly understood. It is often difficult to treat because of the individual’s denial of a problem, difficulties in establishing a therapeutic alliance, and interpersonal and social conflicts. Unfortunately, many individuals with this disorder refuse treatment altogether. Available research suggests that 50% of patients who are adequately treated achieve a symptom-free recovery, while 90% of patients demonstrate at least some improvement.

 It has been found that persecutory delusions respond least well to treatment, with 50% improvement rates and 

 Only a handful of studies have used objective outcome measures to evaluate patient improvement during treatment for delusional disorder.

 The best objective measure of adult psychopathology in the world is the Minnesota Multiphasic Personality Inventory-2 (MMPI-2). There have been hundreds of 

 on the MMPI-2 and the treatment of psychiatric disorders.

 Up until now, there has been nothing in the literature that addresses the utility of the MMPI-2 in tracking or documenting treatment effects in delusional disorder.

This case illustrates the effectiveness of the MMPI-2 in documenting patient recovery during treatment for delusional disorder. Practical implications for psychiatrists and other mental health professionals are discussed.

“Mary,” a 42-year-old white female, temporarily lost custody of her 3 children to her ex-husband 18 months ago due to apparent psychotic-level functioning. I was appointed by the court to arrive at a definitive diagnosis and to provide appropriate guidance about her parenting abilities and custody status. (Mary, a pseudonym, has given written informed consent for her case to be included in this presentation. Identifying information about her has been altered to protect her privacy.)

Mary’s primary symptoms included both persecutory delusions and somatic delusions. Her delusions had been present for about 2 years. She believed that her colleagues at work were concocting a scheme to have her fired. She believed that her mother was not her biological parent. Mary also believed that drones were hovering over her home and that someone had installed a camera in her car to follow her. She reported unrelenting somatic symptoms that she attributed to an alien virus that had been planted in her water at home. Because of her delusional thinking, Mary had recently quit her job and was residing with her parents.

Prior to the onset of her delusions, Mary had obtained 2 master’s degrees and had a full-time position. She had a boyfriend, many friends, and her family relationships were intact. She was described as a smart and sweet person. She had been given primary custody of her 3 children at the time of her divorce 4 years earlier; it was not a highly adversarial divorce proceeding. She had no medical problems. She had no family history of psychosis or other psychiatric disorder.

Mary had been seeing a psychiatrist for several months prior to my involvement in the case; I obtained her records from him. Mary was described as having depression and anxiety. Psychosis was not noted. She was being treated with fluoxetine 20 mg and bupropion hydrochloride extended-release tablets 150 mg, but she was not improving. Mary had not divulged any delusional material to her psychiatrist.

Clinically, Mary was appropriately attired and well-groomed for her sessions with me. She wore make-up and jewelry. She was pleasant with me and made good eye contact. Mary’s cognitive abilities were intact. Her affect was slightly dysphoric but within normal limits. She was not manic or hypomanic. Mary’s delusions were prominent, and she had little or no insight into their nature and severity. She was also suspicious of me; she thought I might be involved in the conspiracy with her colleagues at work.

I asked Mary to provide a urine screen to rule out substance abuse. Her urine screen the same day was negative for illicit drugs.

Mary completed the MMPI-2, answering all 567 questions in 90 minutes. Her responses were scored on 3 validity scales, 10 basic clinical scales, and the PSY-5 supplementary scales.

Mary showed considerable distress but in the context of normal validity scales. She approached the test in an open and honest fashion. She did not exaggerate her symptoms. She was not defensive or guarded. Her responses were considered valid. She was to be believed.

Ten basic clinical scales were developed to assess different psychiatric conditions and symptoms. See 

 below for a description of the 10 scales. Mary’s 10 basic clinical scales showed significant elevations on scales 6-8-1-3. Scales 6 and 8 were considerably higher than scales 1 and 3.While this profile often indicates schizophrenia, Mary’s history and clinical presentation were not consistent with that illness. In my view, Mary’s MMPI-2 profile was reflective of her persecutory delusions (scales 6 and 8) and her somatic delusions (scales 1 and 3), both components in her psychotic illness.

Supplementary scales are available on the MMPI-2 as well. Mary’s PSY-5 scales showed a significant elevation on the scale having to do with psychosis. This was corroborative data to Mary’s 10 basic clinical scales.

Based on her history, clinical observations, and MMPI-2 test data, I diagnosed Mary with delusional disorder. Her delusional disorder was primary. She did not have a comorbid condition, such as bipolar disorder or schizophrenia. Mary did not have major depressive disorder or an anxiety disorder nor was she abusing alcohol or drugs.

No specific stressors were identified that contributed to the onset of Mary’s delusional disorder. However, she was feeling “pressure” from juggling a full-time job with raising 3 children.

Interestingly, Mary’s psychiatrist and I independently but simultaneously came to the conclusion that she had delusional disorder. Mary was started on ziprasidone 20 mg. Fluoxetine 20 mg was continued. A brain MRI at that time was negative. Bupropion was stopped because it enhances dopamine levels and can 

I re-evaluated Mary 4 months later in preparation for her upcoming court appearance. The court would want to hear about my findings and conclusions as well as any progress in her condition since her last court hearing. I interviewed Mary on 2 occasions. She completed the MMPI-2 again, and I obtained updated records from her psychiatrist.

After 4 months on ziprasidone, Mary was remarkably improved. She was tolerating it well, and her delusions had remitted. She had developed important insight about her resolved delusions. They now seemed foreign and distant to her; they did not make sense to her. She could not even recall her suspiciousness about me. Mary’s affect was bright. She was talkative and expressive. She was appreciative of everyone’s concerns. Mary was looking for a full-time job and planned to get her own apartment.

Mary’s MMPI-2 after 4 months of treatment was remarkable as well. It was completely normal. Her validity scales were normal. All 10 basic clinical scales were normal; there were no significant elevations. In fact, there were no near-significant elevations. Her PSY-5 scales were normal as well. All signs of psychosis had dissipated.

Mary will be maintained on ziprasidone for the foreseeable future. She will have monthly to quarterly visits with her psychiatrist. Cognitive behavior therapy has been added to her treatment regimen, since it is regarded as a 

 Mary’s legal case is close to resolution. With her regained parenting abilities, the parties are approaching a compromised settlement.

This case study illustrates many important clinical and practical points.

Mary’s persecutory delusions and somatic delusions both abated with treatment. This result is consistent with the literature that reports that 50% of patients treated adequately achieve a symptom-free recovery.

 Delusional disorder in this case was treated successfully with antipsychotic medication (ziprasidone 20 mg). This finding is contrary to the data that suggest that persecutory delusions are recalcitrant.

condition, and the absence of comorbid conditions may make successful treatment of delusional disorder more attainable.

Overall, Mary’s recovery was likely due to a combination of the relatively short duration of her delusions (about 2 years), the lack of a comorbid condition, the use of an antipsychotic medication, the discontinuance of bupropion, and her high level of premorbid functioning.

The MMPI-2 proved to be a sensitive outcome measure in evaluating this patient’s improvement. Using the MMPI-2 at the time of diagnosis and later during treatment is an objective, data-driven way to assess a patient’s response to treatment. The MMPI-2 can be administered easily and is not overly intrusive.

Lessons learned from this case study are clinically interesting, but only suggestive. Well-designed research is needed to study the proposition that the MMPI-2 is a highly effective instrument for evaluating treatment outcome in delusional disorder.

Mary’s psychiatrist and I worked independently but in a cooperative fashion. This was quite helpful in facilitating Mary’s evaluation and treatment with minimal delays and roadblocks. The sharing of findings and conclusions between us led to an excellent result after much initial confusion.

Mary was fully adherent with her evaluation and treatment, whereas many patients with delusional disorder refuse treatment. Mary’s successful treatment was largely attributable to her therapeutic alliance with her psychiatrist and me. Her motivation to get well superseded any desire to resist intervention. 

 is a critical building block in adequate treatment.

Whether Mary will have a recurrence in her delusional disorder is unclear. Longitudinal research is needed to address the question of incidence recurrence in this specific illness. With other types of psychotic disorders, 

 As such, maintenance treatment in delusional disorder becomes extremely important. Treatment should include a combination of psychiatric medication and individual therapy.

The impact of psychotic disorders on child custody cases is a delicate matter. It should be recognized by all parties that a parent’s recovery from a psychotic disorder may be less than permanent. Child custody decisions need to be made with that psychiatric reality in mind. Maintenance treatment for the parent with a psychotic disorder is the vehicle by which parenting abilities can be regained and sustained.

is a clinical psychologist in private practice in Birmingham, Alabama. He is clinical associate professor, department of psychology, University of Alabama at Birmingham. Much of his clinical practice is devoted to forensic cases, including child custody, personal injury, and criminal cases.

1. Bourgeois JA. Delusional disorder: Overview, diagnosis, epidemiology. 2017. 

Acute and transient psychotic disorders versus persistent delusional disorders: a comparative longitudinal study

3. O’Connor K, Stip E, Pélissier MC, et al. Treating delusional disorder: a comparison of cognitive-behavioural therapy and attention placebo control. 

4. Butcher JN. Significant contributions for use of the MMPI/MMPI-2 in treatment. 2016. 

https://pdfs.semanticscholar.org/cd97/a44d879d3db42721556ca74588543aa68227.pdf

5. Kesby, JP, Eyler, DW, McGrath, JJ, Scott, JG. 

Dopamine, psychosis and schizophrenia: the widening gap between basic and clinical neuroscience

Current treatments for delusional disorder

7. González-Rodríguez A, Molina-Andreu O, Odriozola VN, Ferrer CG, Penadés R, Catalan R. Delusional disorder: An overview of affective symptoms and antidepressant use. 

Recurrent acute and transient psychotic disorder: A pilot study

9. Deutsch RM, Clyman J. Impact of mental illness on parenting capacity in a child custody matter. 

10. Engur B. Parents with psychosis: Impact on parenting and parent-child relationship. 

Journal of Child and Adolescent Behavior. 

This case illustrates the practical implications and effectiveness of the Minnesota Multiphasic Personality Inventory-2 in documenting patient recovery during treatment for delusional disorder.

Documenting Recovery in Delusional Disorder With the MMPI-2

A 59-year-old man with a history of multiple concussions has been having a series of neurocognitive symptoms for the past several years. Discover more in this case.

4 Stages of Chronic Traumatic Encephalopathy

Lack of empathy is a commonly known feature of narcissistic personality disorder. Relationships are typically shallow and difficult to maintain. What are some other features of NPD? More in this case presentation.

10 Things to Know About Narcissistic Personality Disorder

Despite advances in addiction research, substance use disorders continue to tighten their grip on society. Forensic psychiatrist and Editor in Chief Emeritus of 

 James L. Knoll IV, MD, weighs in on a case report.

A Rock and A Hard Place, by Eduardo Constantino, MD

Dr Constantino has our gratitude and sincere respect for submitting his case which is both real world and timely. Upon consulting with many respected addiction psychiatrists to formulate my response, all of them added that they were grateful that these difficult issues were being raised for discussion. I must imagine that such cases will be seen with greater frequency, particularly as the specialty of addiction psychiatry advances and substance use disorders tighten their grip on society.

In my view, Dr Constantino’s case is not so much a case about malpractice, but an extremely rich case highlighting the ethical and legal duties of a practicing addiction psychiatrist. There do not appear to be any clear deviations from the standard of care, nor are we made aware of any damages-effectively removing two of the 

that a plaintiff must prove in a malpractice case.

 Nevertheless, the learning value from this case is substantial. Dr Constantino’s “awkward quandary” involved the frustrating dilemma between preserving a patient’s right to confidentiality-and an ethical/clinical duty to act beneficently and preserve life. Yet as with many clinical dilemmas, the resolution often lies along the path of engagement and dialogue with the patient.

All physicians are presumed to have some awareness of confidentiality, given that it is required by professional ethics, hospital policy, and federal and state law. The exceptions to confidentiality are relatively small in number and include: medical emergencies, statutory reporting requirements (suspected child or elder abuse) and an individual state’s legal requirements regarding patients’ credible threats to third parties (Tarasoff statutes). From a legal standpoint, actions for breaching confidentiality may include: breach of contract, breach of statutory duty and professional misconduct. Confidentiality and privacy of psychiatric records is especially important in the field of addiction psychiatry. In fact, this issue is stressed by federal law, which requires that documentation in addiction treatment be held to even higher standards of confidentiality than general psychiatric and medical encounters.

 (AAAP), a “basic principle of confidentiality of personal health information is that, to the greatest extent possible, control of personal medical information should be in the hands of the patient. Nonetheless, when patients receive . . . substance use disorder services, their agreement to begin treatment should include their written consent that certain identifiable health information will be shared with other health professionals.”

A major concern of patients and addiction psychiatrists is that failure to maintain strict confidentiality in the setting of substance use treatment can potentially result in a cascade of highly adverse consequences.

 For example, it is not uncommon for disclosure of substance use treatment to result in: loss of employment, loss of child custody, discrimination by insurers and other health care professionals. Of course, the possibilities of arrest and incarceration are ever-present. Unsurprisingly, such concerns may lead individuals in need of treatment to avoid seeking the help they need-often until it is too late. Keeping this in mind, let us turn to Dr Constantino’s first question: “

Even though his probation officer was allowed to speak to any and all medical staff, could we legally call the probation officer against the patient’s specific instructions?”

Based on the case description, the treatment team’s decision to not call the probation officer seems appropriate, as doing otherwise would be a violation of consent and breach of confidentiality. It is recommended that psychiatrists obtain specific signed consents “for release of any personal health information to entities outside of the health-care delivery system, such as . . . judges, prosecutors, police or other legal investigators, or institutional or community corrections officials, even in response to subpoenas, as stipulated in 42 CFR Part 2.”

 Absent patient consent, requests for information from law enforcement or other government agencies seeking information without patient consent should be denied. One exception to this may be a specific court order (per 42 CFR Part 2). However, such court orders are typically reserved for patients who have been involved in serious crimes.

Addiction specialists know that parole and probation officers play a critical role in the lives of their patients. A positive relationship with a parole officer can mean the difference between recidivism-and continued wellness in the community.

 Because of their central role, it is important to have a clear understanding, from the beginning of treatment, about the precise conditions of probation that were ordered by the court. A meeting with the probation officer may be helpful to establish rapport, ground rules, limits of confidentiality and to review any legal documentation from the court. A reliable understanding of the probation officers’ “marching orders” will put the treatment team in a better position to understand any concerns the probation officer may have, as well as what information may be communicated between parties.

Turning to Dr Constantino’s second and third questions regarding notifying the patient’s IOP, and concerns about providing appropriate care-it is noted that the patient refused to give consent to speak to his IOP substance use treatment center. From a clinical standpoint, effective coordination of care is assumed to be in the best interests of the patient. Yet in this case, it can be argued that the same legal restrictions apply to informing the patient’s IOP. This is highly unfortunate, but there appear to be at least two barriers. First, the patient refused to give consent. Second, there is no mention that consent was legally applied by the court to the patient’s original terms of probation, which would allow for communication of health information with the IOP and vice versa.

There are several important points to consider regarding this impasse. The AAAP notes that when patients opt to not allow health information to be shared among other providers, they “should be educated about the implications for the quality of the health care services they may receive, and thus the potential detriments to their own health care outcomes and health status, when they decline to sign the consent.”

 Therefore, an open and serious discussion with the patient regarding the potentially life-threatening consequences of refusing to allow communication between mental health and substance use treatment providers should be undertaken and documented. However, the patient is noted to have poor insight into his dilemma and so we proceed to other options for now, while recognizing that improving insight will remain a continuing goal.

Arguably, the ideal resolution occurs prior to any treatment plan implementation, and involves a clear agreement between patient and treatment team from the outset regarding coordination and communication of care with the IOP. The patient’s signed informed consent for communication with other health care providers is one of the goals of this discussion. Some addiction specialists would advise going no further with a treatment agreement if the patient refuses to allow communication between key health care providers. In contrast, other addiction psychiatrists may view their ethical and clinical duty to the patient as transcending this impasse and would not refuse treatment to a patient who refused to give consent to communicate with other health care providers.

Finally, a third option involves investigating, with legal counsel, the possibility of returning to court to amend the patient’s probation conditions to allow for such communications. This last option would be less preferable, of course, to the patient agreeing with his treatment team to give consent. In other words, a solid and agreed upon plan from outset is superior to one that must confront repeated barriers to coordinated treatment. Nevertheless, there may be no simple or clear-cut answers, as obtaining consent in advance does not preclude a patient from later deciding to rescind consent. What are some possible adverse outcomes if a psychiatrist decides (in good faith) that a duty to the patient necessitates contact with a key health care provider, despite the patient refusing to give consent? A medical malpractice suit brought forth by the patient for breach of confidentiality is one possibility. In such a case, the patient would need to show that the breach of confidentiality directly caused some untoward event (eg, loss of employment, loss of custody, psychological damages.). Another possibility is that an aggrieved patient may lodge a formal complaint with the local medical board, prompting a review and possible sanctions.

This case highlights the growing importance of addiction psychiatry, as well as appropriate legal arrangements 

 of treatment to ensure proper coordination of care. Addiction psychiatrists know well that substance use and criminal recidivism are irrevocably linked,

 and that relapse prevention is necessary to prevent a return to jail or prison.

 For justice-involved individuals with substance use disorders, continued illicit drug use likely inhibits the ability to “mature out” of a criminal lifestyle in young adults.

 The stakes are extremely high for this population of patients. Release from prison is associated with significant mortality rates and a leading cause is drug overdose.

 The first two weeks after release appears to be a particularly vulnerable time of high risk for opioid overdose.

Dr Constantino is appropriately concerned about the challenge involved when a prolonged period without opioid use can simultaneously be a sign of recovery, as well as a risk factor for fatal overdose.

 I would add that the patient’s focus on getting through his “five months” of probation and refusal of long acting naltrexone would reasonably make a treatment provider nervous. There is now some data supporting extended-release naltrexone being associated with a decreased risk of overdose. Thus, naltrexone is currently an option for patients who decline or are unable to obtain opioid agonist treatment.

 This can become critical in that opioid use disorder treatment remains quite limited in US correctional facilities.

 Looking towards the future, it is hoped that concerted efforts are made to implement programs across the criminal justice continuum to address this deadly public health issue.

Dr Constantino and his team seek consultation from their risk management department-always a sound decision that follows the dictum of the great Tom Gutheil, MD: “Never worry alone.” Finally, I would add that Dr Constantino’s team appeared to exert due diligence with “repeated” follow up calls and a letter. This is particularly important in that proper termination with patients involves such efforts, along with documentation they occurred and that some other potential providers in the community were offered to the patient. In this case, a follow-up communication letter letting the patient know you are willing to arrange communication of important health care information with his new provider would be ideal.

I conclude again with a thanks to Dr Constantino, as well as a supportive proclamation that competent and evidence-based substance use disorder treatment “is a more appropriate intervention than incarceration for non-violent drug offenders,” and “non-violent drug offenders should be diverted to treatment programs while being monitored through intensive probation drug courts, or other means, instead of expensive and less effective incarceration.”

 Further, treatment and monitoring following incarceration should be available, and likely court mandated, for those on probation to prevent relapse, deadly overdose and recidivism.

Dr Knoll would like to thank Professor Andrew J. Saxon, MD, Director, Center of Excellence in Substance Abuse Treatment and Education, University of Washington School of Medicine, for his helpful review and comments.

Dr Knoll is Director of Forensic Psychiatry and Professor of Psychiatry at SUNY Upstate Medical University in Syracuse, NY. He is Editor in Chief Emeritus of

James L. Knoll IV, MD, analyzes the ethical and legal duties of psychiatrists treating substance use disorders.

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