Slideshows

Some speculate the pharmaceutical industry has virtually abandoned new drug development in neuroscience with a few exceptions. However, it should be noted that progress has been made.

13 Psychiatric Drugs With Novel Mechanisms: A Timeline

Disordered sleep disturbances associated with alcohol use disorders (AUD) can 

for several years, even when patients experience sustained recovery.

 One naturalistic, longitudinal study found that over 60% of patients with alcohol dependence and insomnia at baseline continue to have insomnia at 6 months, regardless of current alcohol use status (abstinent, moderate, or heavy drinking).

When evaluating treatment options in these patients, there are differential considerations compared with patients with primary insomnia without 

 comorbidity, including reducing risk of alcohol relapse as well as abuse issues with some pharmacologic agents. Indeed, sleep disturbance is associated with alcohol relapse risk after a period of abstinence.

of addiction medicine physicians, only 22% offered pharmacological treatment to more than half of patients with sleep problems in early recovery from AUD.

 reviewed current and potential pharmacologic treatments for patients with insomnia and alcohol use disorders. Study authors searched Medline, EMBASE, and PsycINFO from 1990 through December 2019. They included studies that prospectively evaluated drug effects on insomnia-related sleep parameters in participants with alcohol disorder who were treatment-seeking or abstinent at study entry

The authors also attempted to identify novel molecules in development in the United States that may be useful in the treatment of insomnia. The authors screened 190 abstracts and reviewed 36 full-text articles for eligibility. A total of 18 studies (15 randomized controlled trials [RCTs] and 3 open-label studies) were included, including studies of antidepressants, anticonvulsants, melatonin agonists, and antipsychotics.

Trazodone 50 mg to 200 mg/day was shown to improve sleep in two RCTs, although 1 study showed evidence of an increased risk for alcohol relapse. Overall, trazodone is the most frequently prescribed medication for the treatment of 

One double-blind active comparator trial found evidence for significant improvements in sleep quality in patients with mild-to-moderate alcohol withdrawal for treatment with carbamazepine (versus lorazepam).

Six RCTs have evaluated the efficacy of gabapentin 400 mg to 1800 mg/day. Three of these trials showed significant improvements in sleep parameters, and 4 showed a positive effect on drinking outcomes. The authors noted that gabapentin is non-hepatically metabolized, does not lower seizure threshold, and does not require blood monitoring, although it has been associated with abuse liability and suicidal thoughts and behaviors.

A small, open-label, 4-week study found improvement in sleep parameters with 8 mg ramelteon. Another small, open-label, 6-week study found improvements in subjective sleep quality with agomelatine 25 mg to 50 mg/day. The authors noted that agomelatine has potential hepatoxicity and is not approved by the United States Federal Drug Administration (FDA).

Two placebo-controlled RCTs found that quetiapine at doses up to 400 mg/day significantly improved sleep parameters in patients with AUD.

Two RCTs showed significant improvements with acamprosate in patients with AUD during abstinence.

In a 13-week RCT in veterans with post-traumatic stress disorder and comorbid AUD, prazosin 16 mg/day did not improve sleep parameters or alcohol use compared to placebo.

One placebo-controlled RCT found that the tumor necrosis factor-alpha blocker etanercept at 25 mg significantly reduced the amount and percentage of REM sleep.

The authors identified 8 novel compounds currently being studied in the United States. Three of these agents target the orexin system. Another compound targets gamma-aminobutryic acid receptors. Piromelatine, a melatonin and serotonin agonist is in development for sleep disorders and Alzheimer disease. The atypical antipsychotic lumateperone is also being studied in Phase 2 trials for sleep disorders associated with neuropsychiatric disorders. A nociceptin/orphanin-FQ receptor agonist is also being evaluated in a Phase 2 study in adults with AUD.

The authors note that the prevalence of insomnia in patients with AUD is high, but there is limited data on the persistence of sleep-related disorders for patients with AUD who are in sustained remission. The use of sedative-hypnotic agents (eg, benzodiazepine receptor agonists) are limited due to risk of abuse liability, overdose, and alcohol relapse in this patient population. There is some evidence for other pharmacologic interventions, although these have not been extensively studied and are not approved by the FDA, and several other agents are in development.

There is a need for safe and efficacious treatment options for vulnerable patients with AUD in early and sustained recovery. The following cases serve to illustrate scenarios that could take place in clinical practice. The cases are for illustrative purposes and the identity and details of patients have been changed.

“Mr J” has a longstanding history of schizophrenia and severe AUD, currently with 2 years’ sobriety. His psychosis is currently stable on quetiapine 300 mg nightly, but he reports worsening insomnia over the past 2 months resulting from anxiety associated with the coronavirus pandemic. He has remained abstinent from alcohol but expresses concern about a relapse of drinking. His psychiatrist increased his quetiapine to 400 mg nightly. Over the following month, his insomnia abated, though he noted increased appetite with an associated 3 lb weight gain.

“Ms K” has a 10-year history of moderate AUD and comorbid fibromyalgia. After 3 years of sobriety, she relapsed on alcohol. One month after alcohol detoxification, she noted onset of initial and middle insomnia. Her psychiatrist subsequently initiated treatment with gabapentin 300 mg nightly, and she noted subjective improvements in insomnia and sleep quality, as well as mild improvements in her pain levels.

“Mr M” is a 22-year-old male currently in a long-term residential treatment facility following a first hospitalization for severe AUD. He has been in residential treatment for 2 months. Although he has noted sleep disturbance since he completed alcohol detoxification, he recently reported symptoms of middle and terminal insomnia to his physician. He was prescribed trazodone 50 mg nightly. In the first month of treatment, his insomnia resolved, though he had a slip and consumed 1 alcoholic beverage.

 is professor, Department of Psychiatry and Health Behavior, Augusta University, Augusta, GA. He is the Schizophrenia Section Chief for 

 The author reports that he receives research support from Augusta University, the National Institute of Mental Health, the Brain and Behavior Research Foundation, and the Stanley Medical Research Institute.

1. Chakravorty S, Chaudhary NS, Brower KJ. 

Alcohol dependence and its relationship with insomnia and other sleep disorders

2. Brower KJ, Krentzman A, Robinson EA. Persistent insomnia, abstinence, and moderate drinking in alcohol-dependent individuals. 

3. Arnedt JT, Conroy DA, Brower KJ. Treatment options for sleep disturbances during alcohol recovery. 

4. Friedmann PD, Herman DS, Freedman S, et al. 

Treatment of sleep disturbance in alcohol recovery: a national survey of addiction medicine physicians

5. Roehrs TA, Auciello J, Tseng J, Whiteside G. Pharmacological treatment options for insomnia in patients with alcohol use disorder in recovery. 

6. Schubert JR, Arnedt JT. Management of insomnia in patients with alcohol use disorder. 

Articles

Clinical considerations for evaluating treatment options for patients with insomnia and AUD versus patients with primary insomnia without substance use comorbidity.

Understanding Comorbid Insomnia and Alcohol Use

It is hard to believe it is already August. Soon children will return to school, in 1 form or another; the days will grow shorter and colder, and the leaves will change color. To some it marks the end of summer, and to others it marks the beginning of the autumn holidays and cozier days. It depends on how you look at it.

Several of this month’s contributors share these sentiments, reminding us that both the half-full and half-empty views can serve as important wake-up calls. In our 

, the authors celebrate advances in cancer care, but they also recognize we can do more to help patients. For instance, Wendy G. Lichtenthal, PhD, and colleagues explore how meaning-centered psychotherapy (MCP) can serve as a buffer against the depression and hopelessness reported by patients with metastatic disease. According to the authors, this brief, structured, manualized intervention enhances patients’ sense of meaning and purpose by reflecting on what matters most to them and facilitating reconnection, even during the most challenging of times. Similarly, Lawrence E. Kaplan, DO, sheds light on the lingering neuropsychiatric sequalae, either due to the specific cancer or adverse effects of treatment. With improved screening and awareness, interdisciplinary approaches and interventions can address these issues to improve patients’ lives.

Similarly, in the front cover article discussing racism, 7 psychiatrists come together to challenge the status quo. We can—and should—do better, they say. Not only do the authors identify areas that need to be addressed, but they provide measures to help us ensure we are indeed moving forward.

Also in this issue, leaders in psychiatry discuss the need to push the envelope to do more for patients. Jerald Kay, MD, and Joel Yager, MD, lament the 

 often seen in psychiatric literature. After diagnosing the problem, they share potential cures, identify future steps to remedy the situation, and challenge the field to do better.

, agrees with many of those sentiments, he reminds us of the 

. From pharmacogenomics to neuroimaging and brain circuitry, ever-evolving research propels psychiatry into new areas to improve patient care and outcomes. His “glass half full” assessment reminds us that while progress has been made, we need to continue pushing for more.

With everything going on in the world, this lesson has become abundantly clear—our attitudes will help us ride the ups and downs and the slings and arrows that present themselves and propel us to better times. And, we hope, this issue of 

will provide you with the tools and knowledge to achieve successes for you and your patients. ❒

With everything going on in the world, this lesson has become abundantly clear—our attitudes will help us ride the ups and downs and the slings and arrows that present themselves and propel us to better times.

The Glass Is Half Full

Despite advances in clinical care for patients with cancer, distress and depression continue to haunt patients. These fast facts will help you better understand and care for patients with cancer. 

5 Fast Facts for Addressing Distress & Depression in Cancer

According to the Centers for Disease Control, about 6.1 million children in the United States have been diagnosed with attention-deficit/hyperactivity disorder. While the number of available agents has grown over the years, many options have harsh side effect profiles or do not fully address the symptoms.

Results from a phase III randomized, placebo-controlled study of a new agent showed promise of a safe and effective new treatment option. The results appear in 

Mental Health Minute, Andrew Cutler, MD, shares highlights of the SPN-812 study. Cutler is a trial investigator and clinical professor of psychiatry, 

Cutler explains the agent, a multimodal serotonergic and noradrenergic modulating agent and non-stimulant medication, was successful in in improving symptoms of ADHD in children and met both primary and secondary outcome measures. In addition, he notes efficacy was seen as early as one week after initiating treatment, which is unlike many of the other treatments available. The agent also appeared to be well tolerated.

, SPN-812 has PDUFA target action date of Nov. 8, 2020.

Videos

Andrew Cutler, MD, shares insights on the results of a Phase III trial that shows great promise in the treatment of ADHD. 

Promising New Treatment for ADHD

Many experts predict a sharp rise in psychiatric emergencies as the nation emerges from sheltering-in-place, especially since individuals are dealing with unprecedented stressors and have been unable to access traditional treatment settings. Mental health crises may be one area in which therapeutic professionals might be a logical substitute for traditional police interventions. But what services comprise the crisis spectrum of care? And, if you treat patients in a private office or clinic, how might you best access these services when you encounter a psychiatric emergency?

Crisis services for behavioral health emergencies may include a wide variety of approaches, and they tend to vary depending on your state, county, or community. Yet, there are general overall concepts applicable to most crisis programs and their target patient populations.

A mental health crisis is a situation in which a person’s thoughts, emotions, and behaviors can put them in jeopardy of harming themselves or others and/or put them at risk of being unable to care for themselves or access food, clothing, and shelter. Crises also include acute conditions that could quickly deteriorate into dangerousness or inability to care for self, even if those issues do not currently pose a problem.

A mental health crisis can surface anywhere—in public, in the home or work environment, or in any number of clinical settings. This discussion will focus on the considerations when an apparent crisis arises in patients under a clinician's direct care.

The following questions will help determine if a mental health crisis exists and if crisis services should be accessed 

1. Due to their behavioral health conditions, is this individual acutely dangerous to self or others, or unable to care for self?

2. If the answer to question 1 is not clear, are there concerns that, without prompt intervention, the behavioral health situation could evolve into dangerousness or inability to care for self?

If the answer to question (1) or (2 ) is “yes,” then answer (A) and (B) below.

A. Is this condition unlikely to be resolved by interventions without the need for a higher level of care?

B. Even if our interventions can temporarily stabilize the situation, is there a high degree of concern that dangerousness or inability to care for self will return shortly after our contact has ended?

If the answer to (A) or (B) is “yes,” then there is a crisis situation requiring acute external interventions.

Determining dangerousness and/or inability to care for self

The clinician should consider several factors when assessing a patient for dangerousness and ability to care for self.

. Is this the first time you have met with this individual, or are they well known to you?

. How certain are you about the veracity of their statements? Do you believe them when they say they will follow through with a plan?

. What is your understanding of how they have acted when experiencing similar behavioral issues in the past?

. Has this person made suicide attempts or become aggressive in the past?

. What do family, significant others, co-workers, and caregivers say about the patient’s current behavior and their concerns about these behaviors?

There are a number of things to keep in mind when a patient appears to be in a psychiatric crisis.

When possible, voluntary engagement is best. 

A willing, cooperative patient who understands their treatment goals and plan almost invariably has better outcomes than someone forcibly detained and transported involuntarily. If safe to do so, collaborate with patients on an appropriate plan that they find agreeable. The least restrictive, voluntary setting for crisis care should also be targeted in this way.

 Always choose the option that ensures your patient will safely reach the intended destination. It is far better to have temporarily involved police than to have an individual go missing, fail to arrive for treatment at the emergency program, or jump from a moving vehicle en route to help.

. Patients may talk about past thoughts or fantasies of dangerous behaviors. Do not immediately call 911 just because a patient says the word 

 or offhandedly mentions a thought of killing another out of frustration. Carefully explore what the person is saying before determining the need for referral to a higher level of care. Of course, always err on the side of safety.

. Therapists might be reluctant to engage emergency services or obtain an involuntary hold because they are concerned their patient will feel betrayed. Although an individual might initially be angry, in most cases, they will later be very thankful that you cared, intervened, and saved their life.

Upon initiation of treatment relationship, obtain signed consents from all your outpatients so you can stay involved during and after any crisis.

 It is a good idea to have all your patients sign a general consent allowing you to be informed of their assessment, treatment, and disposition within crisis services. A signed consent transmitted to a crisis program will allow that program to involve you in the care of your patient while respecting HIPAA privacy laws. However, it is important to note that the patient can always choose to rescind any previously signed consent.

Be familiar with your community/county resources before you encounter a crisis

. Trying to determine resources in the heat of the moment is already far too late. Be aware of the voluntary and involuntary crisis services available in your community before you are faced with a crisis.

These considerations and questions help to determine the acuity and level of intervention needed. For example, an initial meeting with reported symptoms requires a different level of evaluation than if the patient and their symptom history are well-known to you. Similarly, a patient that is well-known who reports a sudden change or demonstrates a marked difference from their usual behavior should raise the level of acuity. Based on familiarity, you must evaluate your level of trust with the patient. If trust is nebulous, then it is paramount to delve into collateral opinions of family and significant others. Concerns may first arise from a patient’s report, their significant others’ report, or your personal assessment. Regardless of the source of the initial warning, the response should be comparable.

Although an individual’s mention of the word 

 in discussing previous thoughts or incidents may not be considered a reason for accessing crisis services, any concern that patients may be at risk to harm themselves should be considered a reason for action. It is most important to learn about an individual’s thoughts around suicide, especially if there is any suicidal plan or intent. To determine if a patient needs a higher level of care, clinicians should consider the following issues. 

 Is the person thinking/talking about suicide, or saying that death seems to be an option, or expressing that the world would not miss them/would be a better without them?

 Does the person have a specific idea about how they would kill themselves? How lethal is this method?

 How much does the person want to use a particular method to kill themselves? How serious are they about it?

 Does this individual have access to the means they have described to kill themselves?

 Does the person have strong religious or cultural beliefs that forbid suicide? Do they have others who rely on them that they feel they cannot leave?

Chronic symptoms of psychosis may be a well-controlled part of an individual’s life and not necessitate an emergency referral. Acute psychosis, however, may lead the patient to harm themselves or others or may cause an inability for them to care for themselves. For example, if the patient is currently stable and the hallucinations are tolerable and not placing the patient at risk, then long-standing auditory hallucinations (eg, a running commentary of what the patient sees) may be fine. On the other hand, a new delusion may necessitate intervention, especially if the hallucinations have negative consequences for the patient (eg, hallucinations dictating all food is poisonous and must be avoided, which results in the patient starving themselves). Similarly, command auditory hallucinations to attack family members or delusions that one has the ability to fly and should jump off a tall buildingare clearly psychiatric emergencies. Thus, there are many issues that must be considered.

 Is the person newly experiencing auditory hallucinations or experiencing a substantial increase in chronic hallucinations? Are the hallucinations commanding them to do things, especially to harm themselves, others, or objects? Are the hallucinations derogatory or highly critical of the patient? Does the patient feel they are unable to resist doing what the hallucinations are telling them?

 Does the person feel others wish to harm them and they might have to defend themselves or preemptively attack others? Does the person believe other people want to kill them? Is the person obsessively fixated on another person who may not share their feelings? Is the patient paranoid or delusional about anything that would prevent them from accessing food, clothing, or shelter (eg, if they go inside they will die, all foods are poisonous, they are impervious to cold and do not require a coat in subzero weather)?

. Has the individual become so confused or withdrawn that they are unable to appropriately interact with others and their environment and, thus, unable to access food, clothing and/or shelter?

When symptoms of mania are uncontrolled, there is risk for harm to self or others as a result of rash judgements, impulsivity, inability to rest, grandiosity, and impaired decision-making. Evaluating the severity of a manic or hypomanic episode may be determined with the following considerations.

 Is the person displaying poor judgment, unable to differentiate between right and wrong, spending money they do not have, placing themselves into dangerous situations unwittingly?

 Is the patient going without sleep or doing specific activities nonstop for long hours?

 Is the person easily angered, lashing out, or easily moved to anguish and sobbing?

, unlike uncontrolled mania, is often more objectively apparent in terms of current intoxication or effects of drug misuse. The severity of substance abuse may be apparent in terms of mood, judgement, or disorganization.

 Is the person despondent about their substance abuse or inability to quit? Have they mentioned suicide?

 Is their current intoxication or level of withdrawal clouding their judgment and putting them at risk?

 Can the person safely leave the facility and get home on their own?

Fortunately, there are a variety of crisis programs that can assist the clinician in providing help for their patient. Programs vary in their level of care and support as well as cost. By becoming familiar with the options in your area, you will be better able to offer information to patients before a crisis occurs as well as when the need arises.

 number is available in most areas; it can be reached via 800-273-TALK. The FCC has approved a 3-digit hotline number—988—to make it easier for people to access mental health resources, which should be available by summer 2022. If you are in direct contact with a patient, you likely will not need to refer them to a hotline; however, you will want to ensure patients are informed about such resources and should add the information to your voicemail message.

. Although technically not crisis programs, many county and municipal programs have a 24-hour mental health line, sometimes called an ACCESS line, to arrange for prompt mental health appointments, referrals, and links to services. These programs can also direct individuals to appropriate 

 These are crisis professionals, typically therapists or social workers, who will go to an individual in crisis for an onsite assessment. When possible, they will attempt to de-escalate and stabilize the patient at the site, so the patient does not need to be moved offsite to access a higher level of care. Based on the assessment, mobile crisis teams will often transport patients to an appropriate destination, which could be a community crisis center, a psychiatry emergency department (ED), a psychiatric inpatient unit, or a general hospital ED. Mobile crisis models can operate independently or may partner with the police; frequently the mobile crisis team can be accessed via police dispatch.

Community crisis programs/centers/mental health urgent care

. In recent years, many locations around the country have created drop-in crisis facilities. These can range from a simple set-up, like a section of the community mental health clinic staffed with crisis therapists, to a comprehensive crisis center with crisis intervention, 23-hour crisis stabilization units (intensive outpatient stabilization services which typically have a limit of 23 hours 59 minutes—anyone requiring a longer stay is moved to an inpatient unit), and substance abuse and/or detox programs. Patients typically need to arrive voluntarily, but mobile crisis teams, case managers, and police officers can also bring them to these centers. Although they may be able to accommodate involuntary detention patients, including initiation of involuntary holds, these patients are typically transferred to a medical ED or hospital rather than remaining onsite involuntarily.

. Although not available in every region,, a substantial number of locations have Psychiatric Emergency Programs that are designated as the main receiving site for involuntary and high-acuity psychiatric detentions. These programs typically accept voluntary patients and self-presenting individuals, but most patients tend to be involuntary cases that arrive via police or ambulance. These programs offer immediate assessment and treatment (including medication) with 23-hour crisis stabilization capacity. These units are invariably locked, so anyone entering will have to be discharged by a clinician before they can leave. For this reason, it may be the preferred option for individuals who refuse emergency care or who are flight risks.

. Most inpatient psychiatric hospitals accept the majority of their patients via direct referrals from psychiatrists with hospital admitting privileges or via referrals from regional medical and psychiatric EDs. However, many programs have intake hours in which an individual can self-present on recommendation from their outpatient therapist. In such situations, a member of the psychiatric hospital staff will assess for a possible admission to the inpatient unit.

. In the United States, the default location to send a crisis patient is the nearest general hospital medical ED, which is open 24 hours a day and obliged to evaluate any individual who requests services. The numbers of behavioral emergency patients presenting at medical EDs around the country has climbed in recent years, and it is currently estimated that 1 in every 8 patients in EDs 

with a behavioral emergency as the chief complaint.

 Most EDs, however, have little more to offer than a medical clearance, (perhaps) sedating medications, or a referral to an inpatient hospital bed.

A promising trend has been to offer higher levels of psychiatric care in medical EDs, including psychiatric assessment and treatment recommendations via on-demand telepsychiatry. Another new and useful trend is the availability of EmPATH (Emergency Psychiatry Assessment Treatment and Healing) units, which are specialized psychiatric emergency programs affiliated with the ED, analogous to an ICU dedicated for emergency behavioral health patients.

. When there are no other alternatives, calling 911 remains a legitimate best option for activating emergency services. It allows for a patient assessment and transport to a crisis facility or ED. Depending on your community or state as well as the acuity of the emergency, response may be from a crisis team, emergency medical services, and/or police.

 is Vice President for Acute Psychiatry with the physician partnership 

 and Assistant Clinical Professor of Psychiatry, 

is a registered nurse working as Operations Consultant for 

 Psychiatry/Neurology practice line. Dr Zeller and Ms Kircher have no disclosures to report regarding the subject of this article.

1. Kalter L. Treating mental illness in the ED. AAMC. September 3, 2019. Accessed July 27, 2020. 

https://www.aamc.org/news-insights/treating-mental-illness-ed

Inevitably, some of your patients will need of emergency psychiatric services. These tips will help prepare you and your patients when a crisis unfolds.

Understanding Crisis Services: What They Are and When to Access Them

 social distancing story, but it is also a coming of age story.

Whether in the office with face masks, on Zoom without masks, or on the telephone, we have roughly 20 minutes, sometimes less, to perform our routine med-checks. This is unlike an appointment with a chief complaint. In our role of psychiatrist-psychopharmacologist, we use this brief time to evaluate the patient’s response to medication while maintaining a caring and supportive relationship with the patient. It is a routine follow-up where we make necessary medication adjustments; it is a familiar drill that draws comfortably on principles and practices of psychotherapy, especially those of careful listening. It worked for me. Until it didn’t.

Those principles and techniques proved to be false friends. Not only were they not helpful, but they seemed to make things worse. It wasn’t that I was doing something wrong; it was that I could have been doing something better. I could have been maximizing the effectiveness of those check-ups. The problem, it turned out, was my prioritization of the interpersonal relationship in exchange for shortchanging the medication-assessment task. 

 and new ways of interacting shined a light on the verbal communications. It was then that I realized my questions, my attempts to foster the patient-doctor alliance, was actually betraying me.

Before the pandemic, for instance, I began each session with my standard greeting and opening query, "How are you?" Is this not personal and welcoming? Is this not appropriate? I learned that it was not, and here is why.

That popular social greeting, whether via a video, phone, or in person, cues the responder to, “Fine, thank you. How are you?” Too often, that is exactly what happened, but that was not my intention. I then needed to work to get back on track, all the while reminding myself we were meeting to promote healing, not confirm a relationship.

Similarly, some patients replied to that question with complaints unrelated to the prescribed medication, which would similarly derail our appointment; while listening, I also became distractedly 

. Maybe this was good therapy, but it was awful time management and it risked corrupting my medication supervision.

I slowly switched that greeting to, “It’s good to see you” (or something equivalent) followed by, “Let’s get right to business.”

This transitioned into my leading and ever-important question: “Are you taking the meds as I directed?” (Remember, this approach is specifically for scheduled med-check appointments.) Although a brusque and impersonal start, I learned this was necessary; it helped prevent wild-goose chases that followed my incorrect assumption that the patient was both taking the medication and taking it correctly. By taking charge from the start and controlling the agenda of the visit, I was able to promptly uncover important details; it also left adequate time for patient questions and concerns.

That was not the only question causing problems. Take the query, “Are you having side-effects?” Although the question aimed to empower patients, perhaps I was placing too much additional responsibility on them, especially when they were looking to me for help. When someone is not feeling well or not feeling like themselves, they may need someone to pick up the slack. And, many of my patients were not feeling well. Their responses, whether “yes” or “no,” regularly proved incomplete or misleading. As a result, we engaged in a bunch of questions as I aimed to sort out what I was hearing versus what my patients were trying to communicate, only to realize the issues they were presenting were not a result of the prescribed medications. 

I began replacing my side effects question with specific queries tailored to the medications. For instance, I would ask, “Have you felt dizzy?” or, “Have you experienced (insert various likely and unlikely adverse side effects)”? In this way, I was able to help my patients to not only become self-observant but also better understand specific side effects. Thus, I was truly empowering patients and getting the information I needed to best support them.

medication efficacy, I dropped my customary “Are you feeling better?” Here, too, I realized I was getting derailed. There were times when a patient’s report of feeling better was unrelated to the medication. Or, the lack of improvement proved inaccurate. Or, someone was feeling worse not because target symptoms were not going away (they were), but because there were other factors at play.

I asked focused questions, directing my questions toward specific target symptoms. And, I would make it simple by limiting patients to 3 potential choices— “Is symptom ABC worse, better, or the same?”—and seek further details as needed. Then, together, my patient and I could accurately chart treatment progress without being derailed by unreliable impressions. Although I cannot prove it, I think patients became more comfortable saying 

 when they were feeling worse because I introduced that word, as if my speaking it gave them permission to acknowledge it and say it.

I also modified my question toward the end of the med-check visit. Instead of asking, “Do you have questions?” I said, "Now…what are 

 questions?" The former inquiry implied that we were nearing the end of our session, and I was subliminally cuing them to be brief. But time was myissue, not theirs. Why should they be monitoring the time—or be limited by it? The new phrasing implied a subtext of it being theirturn.

The psychiatrist and their patient are a team. Together, we are partners, and that is what partners do. We take turns. Especially now.

Psychiatrist on the Road: Encounters in Healing and Healthcare

, an account of his Locum Tenens experience.

Sometimes our best intentions lead us down the wrong road. By reconsidering a few seemingly harmless questions, this psychiatrist was able to make the most of his medication-check visits with his patients. 

Minefields and Med-Checks: Getting to the Right Questions

 written to help psychiatrists and other health care providers better understand the range of severity of illness that the coronavirus disease 2019 (COVID-19) virus can cause so that they can better explain the facts (as we know them today) to their patients and their families.

The mortality rate reported for COVID-19 has declined since the earliest days of the pandemic. This is partly due to better knowledge about the infection and better protocols that have been developed to treat the more serious forms of the illness. However, arguably the greatest decline in mortality rates is the result of being better able to identify who has been infected with the virus. This increase in identification of infections has increased the size of the denominator, while the numerator has remained relatively unchanged.

Equation 1. Calculation of mortality rate

“Cases” refers to individuals who have been infected with the Sudden Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2).

The calculation of the mortality rate is illustrated in 

, cases of COVID-19 initially were determined by the number of individuals who sought medical attention because of fever, cough, respiratory distress, or other flu-like symptoms and had no other potential causes for these symptoms including not having the seasonal influenza.

 Thus, it was a symptomatic diagnosis, just as it the case with most psychiatric diagnoses. Using this definition of a case, the denominator was smaller than the actual number infected, with the degree of underestimation being a function of how many individuals were infected but either were asymptomatic, did not have sufficient symptoms to seek medical attention, or for some other reason did not seek out care. The degree of underestimation would result in proportional overestimation of the mortality rate based on the 

Case example: A floating, unintentional laboratory experiment

Cruise ships can function as naturalistic research experiments with more controls than is true in clinical practice. The following summary, based on the original report published by 

, details such an example. In May 2020, a trio of Australian physicians and health researchers who traveled on an expeditionary cruise to the Antarctic Peninsula published a report about their experiences in the medical journal 

. Two of the authors, Alvin J. Ing, MBBS (Hons 1 Syd), MD FRACP, and Christine Cocks, were passengers on the cruise, and Jeffrey Green, MD, was a ship physician for this expedition.

In mid-March, the ship departed Ushuaia, Argentina, for a planned 21-day cruise of the Antarctic Peninsula to explore a route similar to the one taken by British explorer Ernest Shackleton in 1915-1917.

No one was allowed on board who had transited through then known hot spots (eg, China, Macau, Hong Kong, Taiwan, Japan, South Korea, or Iran) in the 3 weeks preceding the cruise.

 = 217) were screened for COVID-19 symptoms and body temperature as a condition of boarding.

Multiple hand hygiene stations were positioned throughout the ship, especially in the dining area.

Everyone had daily temperatures taken, which were reviewed by the ship’s 2 physicians.

The first recorded fever occurred in a passenger on day 8.

Isolation protocols were immediately initiated after this discovery. All passengers were confined to their cabins and all were issued surgical masks.

Full personal protective equipment was used for contact with any febrile patients, and N95 masks were worn for any contact between the ship staff and passengers.

By day 14, 5 additional passengers and 4 crew members developed fever, mild cough, and lethargy.

On day 17, one of these passengers, a 68-year-old man who had been a lifelong nonsmoker and had no comorbid medical conditions, deteriorated and required urgent evacuation to a hospital.

Subsequently, 7 additional passengers required medical evacuation: a 70-year-old woman with chronic obstructive pulmonary disease on day 20; a 65-year-old woman with no known comorbid conditions and 2 crew members on day 21; a 68-year-old male (after 15 days of cabin isolation) on day 24, and one of the two ship physicians on day 27.

All the evacuated patients tested positive using reverse transcription polymerase chain reaction (RT-PCR) tests to detect SARS CoV-2 RNA in respiratory specimens.

On Day 20, all 217 individuals onboard were tested with RT-PCR;

128 (59%) tested positive for SARS CoV-2. Of those that tested negative for SARS CoV-19, some were later found to have SARS CoV2 antibodies indicating prior infection.

Of the individuals who tested positive, 104 individuals (81%) were asymptomatic at the time of testing. The other individuals who tested positive (about 1 out of 5) were symptomatic at the time of testing. Of those 24 symptomatic individuals, 16 (two-thirds of the group) had only fever and mild symptoms, while 8 (one-third of the group) had to be medically evacuated. Four of those individuals required intubation and ventilation, and 1 of them died (mortality rate = 0.8% based on 1/128). He was a 50-year-old crew member with no known comorbid medical illness (personal communication, Ing 2020).

: When a population is small (as was true for this cruise ship with about 100 positive individuals), the confidence interval for a rare adverse event (ie, death, which was < 1 out of 100) is large. In such instances, a general rule for estimating the 95% confidence interval is that the upper and lower boundaries would be 3 times higher and 3 times lower, respectively, compared to what was observed. Hence, the estimate of the 95% confidence interval for the mortality rate in this case would be between 2.4% and 0.27% (ie, 0.8% multiplied by and divided by 3, respectively).

Difference in mortality rates based on symptoms versus on the total infected

In the example of the cruise ship, the mortality rate would have been calculated as 4% when the presence of symptoms was required to define a case (ie, 1 death among 24 symptomatic individuals) versus 0.8% when laboratory evidence of infection was sufficient to define a case (1 death among 128 infected cases). The result is a 5-fold difference in the calculated mortality rate depending on whether it was calculated based on symptomatic cases versus all infected cases.

The difference in practice would likely be even greater because mildly symptomatic cases may be missed in clinical practice because asymptomatic patients may not present for medical attention or because their symptoms might be attributed to a common cold or a mild flu-like syndrome. The number of infected individuals on the ship may also have been underestimated, since all 89 individuals who tested negative for actively shedding virus did not have antibody testing. It is possible that some of those who tested negative for actively shedding the virus may have been infected but the virus had already been cleared via an immune response before testing.

While the availability of reliable and valid laboratory tests is a great advance over the early symptomatic-based diagnosis (readers may want to think about the implications for symptomatic diagnosis in psychiatry), the tests can only determine if an individual is actively shedding virus. Obviously, a negative test does not tell us whether the individual will become infected in the future (even within an hour of having the test done) nor does it tell us if the individual has already been infected and has mounted a sufficient immune response to have eradicated the virus. (The first column in this series1 discussed this issue in more detail, along with the need for other reliable and valid tests to identify a history of an eradicated infection that will hopefully convey immunity against the virus—perhaps lifelong as with measles or perhaps much shorter as with seasonal influenza.)

The number of participants in this naturalistic experiment was small, which means that the 95% confidence interval for a mortality rate of 0.8% would be large as previously discussed. However, this caveat does not change the basic observation that the initial mortality rate, by virtue of being based on symptomatic cases, would be several times higher than the true mortality rate with a virus such as SARS CoV-2 because it can produce many mild and even asymptomatic cases.

The mortality rate observed on this ship is consistent with rates observed in the low-risk population discussed in the 

 This population has a low risk of developing an illness that requires hospitalization (

) and a low risk of death (below 1% but nevertheless not zero; 

) from infection with the SARS CoV-2 virus. In contrast, nearly 35% of those who die will be 85 years of age or older. The individuals younger than 85 who die will most likely have comorbid medical illnesses (

For these reasons, it is extremely important to protect high-risk populations via social distancing, the use of masks, and limited contact with anyone nonessential to the health and well-being of these individuals. The experience from this cruise ship also illustrates 2 important factors to consider when endeavoring to protect the vulnerable population. First, there is long incubation period between infection and the development of symptoms (8 days or more). Second, a high number of individuals who are infected are not symptomatic (more than 80% in the case of the experience on this ship).

The media can inform the population, but they can also hype topics to increase audience ratings to drive their revenue as has clearly been the case with COVID-19 reporting (in the author’s opinion). The most recent, egregious example is the focus on increasing numbers of cases, which is directly relevant to the discussion in this series of columns. What the media has not adequately explained (in the author’s opinion) is the nuanced understanding that a rising number of cases may not necessarily be bad but rather could be a positive development—if the cases occur in the low-risk and not the high-risk population and morbidity and mortality remain low. As explained in the second column in this series

 a higher number of low-risk cases could bring us closer to the number needed to achieve community (ie, “herd”) immunity.

Achieving such immunity is an important consideration because a reliable, safe, and effective vaccine has not been developed.While there is hope that a safe and effective vaccine may be available by late this year or early next year, the historical track record suggests it may be years before one is successfully produced for the world population. The reasons for caution relative to vaccines involve many facets, and a full discussion of this issue is beyond the scope of this column. One reason for caution is that vaccines may promote an antibody response that may alone be sufficient to prevent the illness, but it may be that a T cell (lymphocyte) response is also necessary to prevent the illness and that such a response may not occur with some vaccines. In addition, people have to be willing to receive the vaccine. Meanwhile, a recent 

found that 49% of Americans reported that they would be agreeable to vaccination against COVID-19 if such a vaccine becomes available, but 31% were not sure and 20% said they would not be vaccinated.

 Of course, these responses may change as the public becomes more familiar with the illness and more is known about the efficacy and safety of any vaccine.

With that said, there are several important concerns about a strategy of letting the virus propagate through the low-risk population while protecting the vulnerable population. First is the question of how feasible it will be to accomplish this dual goal. For example, grandparents want to see their grandchildren, but the grandchildren may be asymptomatic even though they are shedding the virus. Protecting the vulnerable populations will also be difficult if the current problem of compliance with wearing masks to decrease the spread of the virus in the United States continues.

Second, a small percentage of the low-risk population may be at risk for serious infections, and even death, for reasons that have not yet been identified, or at least not in the public domain. The mortality rate in what should be low-risk individuals is perhaps between 0.01% and 0.1% (

). However, the problem is that those numbers are so small that the 95% confidence intervals will be large, as previously discussed, so that it is difficult to calculate the rate with certainty.

While a difference between 0.01% and 0.1% may seem small, the issue is what such numbers mean in large populations. For example, a major issue is how to re-open schools. There are 72.7 million children 0 to 17 years of age in the United States (www.childstats.gov/americaschilrden/tables/tables/pop1/asp). If the mortality rate in this population is within the noted range, that would translate to between 7270 and 72,700 deaths of children 0 to 17 years of age (ie, the difference between a risk of 0.01% versus 0.1%).

Given these estimates, one must ask: What risk is acceptable (and to whom) to achieve community immunity and save more individuals in the higher risk groups? Or, should that even be a consideration? How does one balance risk when it comes to lives of young healthy individuals versus older and/or unhealthy individuals? These are the type of calculated decisions that Americans have not faced since perhaps World War II. Parenthetically, this discussion illustrates how important it is to know the mortality rate and provides a quite crude example of the type of mathematical modelling of a pandemic that is driving governmental decisions. Currently, it appears that every citizen is free to make these decisions (eg, to wear a mask or not) based on their understanding of the illness and their sense of community responsibility (because wearing a mask protects others more than the life of the person wearing the mask).

Third, little is known about whether and how long immunity lasts after a person has been infected and recovered (again highlighting the problems posed by a novel human pathogenic virus). The assumption is that immunity has occurred with recovery but even that remains to be proven. Beyond that, there is the potential problem that the virus may be able to mutate to overcome immunity. It should be kept in mind that all these caveats also apply to the development of a vaccine. Life is not always straightforward.

Finally, there is little known about whether there are after-effects of viral infection, such as shingles with herpes zoster. What has been established is that the virus can cause damage to other organs beyond the lungs in some (probably small) fraction of those infected. The virus attacks the circulatory system and, hence, can affect any organ in the body even though it probably does so relatively rarely.

New data and an intriguing case example suggest the mortality rate may be decreasing. What does this mean for the days ahead? 