As a psychiatrist, Iâve done countless consults, and one of the most challenging things to explain is that delirium is caused by an underlying medical conditionânot a psychiatric one. Thereâs no specific psychiatric medication to directly treat delirium. Instead, treatment focuses on environmental adjustments, like placing a clock in the room, displaying the date clearly, and providing frequent reorientation to help ground the patient.
One area where psychiatry might make a difference, though, is in addressing sleep issues. Many patients with delirium also have irregular sleep patterns, which is why melatonin is often suggested. However, when orexin antagonists like Suvorexant came on the market, they offered improvements in both sleep quality and quantity without the risky side effects of benzodiazepines and Z-drugs. These medications became a potential option for preventing and possibly treating delirium in various forms.
Recently, Suvorexant underwent a phase-3 trial for delirium prevention, but the results werenât as promising as hoped. While the Suvorexant group did show a lower incidence of delirium in older hospitalized adults compared to the placebo group, the difference wasnât statistically significant. On the bright side, the drug was linked to significantly lower delirium rates in patients with hyperactive and mixed subtypes of dementia, which may open doors for further exploration in these specific cases.
As an inpatient psychiatrist, you encounter a wide array of stories and experiences. Many of my trainees find this to be the most fascinating and engaging part of the job. We have the unique opportunity to delve into the inner workings of the mind and understand the thought processes of patients with serious mental illnesses (SMI). One of the things that often emerges during our evaluations is the presence of various types of delusions. Some are more common than others, with persecutory and grandiose delusions being frequent examples. I often hear patients claim that unknown groups are conspiring to ruin their lives, or a manic patient might declare, “Iâm Jesus Christ.”
Over the years, I’ve noticed that these delusions tend to remain consistent, with similar themes recurring during subsequent admissions. In case youâre wondering, I often see the same individuals with the same issues multiple times a year, giving me a wealth of data points to support this observation. This insight is supported by a recent article from JAMA Psychiatry, which found that delusional content remains consistent across episodes of psychosis. This consistency can help us recognize the early stages of decompensation and potentially intervene before hospitalization becomes necessary. For instance, if a patient claims, “Iâm Jesus Christ” during one episode, it’s likely they will express the same delusion during future episodes.
Another significant finding from this study is the importance of maintaining the intensity of interventions throughout the follow-up period. Unfortunately, there are many reasons why this doesnât always happen, but when it doesnât, poor outcomes are often the result.
After a few years of treating patients with opioid use disorder, it becomes painfully clear how much addiction affects not just the individual but their entire family. Iâm always particularly concerned when a parent with severe opioid use disorder comes in for treatment, especially if they have one or more children. We know that relapse is common, and each instance of relapse carries the risk of death due to the potency of modern opioids.
A recent study explored the heartbreaking question of how many children have lost a parent to an overdose. The findings are staggering: from 2011 to 2021, over 320,000 children lost a parent to an overdose. This loss significantly increases the economic, social, educational, and health burdens on these children, perpetuating a cycle of harm that could affect them for the rest of their lives.
I remember being a resident and having the same question about buprenorphine versus the buprenorphine and naloxone combination. Now, we have a clearer answer. The big question was whether prenatal exposure to the combination of buprenorphine and naloxone, compared to buprenorphine alone, increases the risk of adverse neonatal and maternal outcomes. I was always advised by my mentors to use buprenorphine alone in pregnant patients, as it was considered safer, with concerns that naloxone might pose a risk.
However, an article published in JAMA Psychiatry puts this debate to rest. The study compared perinatal outcomes following prenatal exposure to buprenorphine alone versus the buprenorphine and naloxone combination. The researchers evaluated the risk of congenital malformations, low birth weight, neonatal abstinence syndrome (NAS), neonatal intensive care unit (NICU) admission, preterm birth, and adjusted for confounding factors.
The findings revealed that when buprenorphine combined with naloxone was compared to buprenorphine alone, there was a lower risk of NAS, NICU admission, and being small for gestational age. The other outcome measures were similar for both groups. These results indicate that the risk is comparable, and in some cases, there are more favorable neonatal and maternal outcomes for pregnancies exposed to the buprenorphine and naloxone combination.
I can now confidently tell my former mentors that buprenorphine combined with naloxone during pregnancy appears to be a safe and effective treatment option for mothers with opioid use disorder.
Everyone told me not to comment on this situation a few months ago and here we are:
Recent developments in the case of Matthew Perry’s death have taken a serious turn as two doctors have been charged with the illegal distribution of ketamine. The charges allege that these physicians were involved in prescribing the powerful anesthetic, known for its potential misuse as a recreational drug, outside the bounds of medical necessity.
This case has raised significant concerns about the role of medical professionals in the broader issue of prescription drug abuse. Ketamine, while valuable in certain psychiatric contexts such as treatment resistant depression, carries a high risk of abuse and dependence, making its distribution tightly regulated.
The charges against Perry’s doctors highlight the ongoing challenges in ensuring that powerful medications are prescribed responsibly and underscore the need for stricter oversight in the medical community. The legal proceedings will likely shed more light on the extent of the alleged misconduct and its impact on Perry and others.
The FDA has just approved the first nalmefene auto-injector, a significant development in the fight against opioid overdoses. Nalmefene is an opioid antagonist, like naloxone, but with a longer duration of action. This new auto-injector is designed for easy use by non-medical personnel, making it accessible in emergency situations where time is critical.
The approval of this device reflects the ongoing need for effective tools to combat the opioid overdose, providing another layer of protection for individuals at risk of overdose. With its extended action, the nalmefene auto-injector offers a prolonged response compared to existing naloxone, especially in situations where multiple doses of naloxone might be required.
This innovation will play a crucial role in reducing overdose fatalities, offering hope to communities impacted by the opioid epidemic. As it becomes available, it is expected to be a vital addition to public health strategies aimed at saving lives.
When we think about patients who have trouble regulating strong emotions, it often begins with a genetic predisposition toward higher emotional sensitivity. These individuals experience emotions more intensely than the average person. Their feelings are easily triggered by seemingly minor stressors, and it takes them a long time to return to baseline after experiencing these emotions.
These patients frequently encounter more stressors than the average person, creating a cycle where they experience strong emotions, face excessive stressors, and struggle to re-regulate. This combination makes life particularly challenging for these individuals, who typically lack the tools to cope with their intense emotions effectively.
To exacerbate the situation, these patients often live in invalidating environments. They are surrounded by people who donât understand how distressing it can be to live this way, leading to the development of maladaptive coping strategies. Family and friends may perceive them as âoverly emotional or irrational,â dismissing the severity of their emotional states. As a result, behaviors such as self-injury, drug use, eating disorders, and suicidal tendencies can emerge.
Support from family and friends is often only provided once these maladaptive behaviors have escalated, inadvertently reinforcing these behaviors as useful coping mechanisms. By understanding the underlying genetic and environmental factors contributing to affective dysregulation, we can better support these patients and help them develop healthier ways to manage their emotions.
In the fast-paced world of modern healthcare, it’s not uncommon to encounter individuals who don’t fit neatly into specific psychiatric diagnoses. Recently, I’ve noticed a significant number of patients who, despite not having bipolar disorder or depression, still experience considerable distress. Many of these individuals have endured severe trauma, including sexual abuse, and have a history of self-injurious behavior. I refer to these patients as affectively dysregulated, a term that, while not perfect, attempts to capture their unique experiences.
Treating these individuals is particularly challenging because their core symptoms and experiences often can’t be effectively managed with pharmaceutical drugs. Instead, they require intense psychotherapy, which is typically difficult to find and expensive. This situation often leaves affectively dysregulated patients with few options, leading them to engage in self-harm and seek admission to inpatient hospitals. Unfortunately, this creates a vicious and dangerous cycle, as inpatient units are usually focused on acute stabilization rather than providing the long-term care these patients need.
When evaluating these patients, I try to emphasize the limited efficacy of medications in treating affective dysregulation and instead focus on coping strategies, especially during periods of intense distress. Here are some strategies that can be helpful:
Deep Breathing Exercises: Practicing deep, slow breathing can help calm the nervous system and reduce feelings of panic and anxiety.
Grounding Techniques: Grounding involves using the five senses to reconnect with the present moment. This can include focusing on the feeling of your feet on the ground, listening to ambient sounds, or touching a familiar object.
Mindfulness and Meditation: Mindfulness practices encourage staying present and accepting one’s emotions without judgment. Meditation can also help in cultivating a sense of inner peace and stability.
Physical Activity: Engaging in physical exercise, whether it’s a walk, yoga, or a more intense workout, can help release built-up tension and improve mood.
Creative Outlets: Activities like drawing, painting, writing, or playing music can provide an emotional release and a way to express feelings that might be difficult to articulate otherwise.
Social Support: Talking to friends, family, or support groups can provide comfort and perspective. It’s essential to feel understood and not alone in your struggles.
Professional Help: Seeking therapy from a qualified mental health professional can provide structured support and coping mechanisms tailored to individual needs.
Healthy Distractions: Engaging in hobbies or activities that you enjoy can provide a temporary respite from overwhelming emotions.
Self-Compassion: Practicing kindness towards oneself, especially during tough times, can reduce self-criticism and foster a sense of resilience.
Safety Planning: Having a safety plan in place, which includes identifying triggers, safe people to contact, and safe places to go, can be crucial during times of crisis.
It’s crucial to remember that coping strategies are highly individual, and what works for one person might not work for another. Encouraging patients to explore and find what resonates with them is key. By focusing on these strategies, we can provide affectively dysregulated patients with the tools they need to manage their distress and break the cycle of self-harm and hospital admissions.
Treating agitation is a big part of inpatient and emergency psychiatric treatment. In the emergency department agitation accounts for 2.6% of total patient encounters. Knowing which medications to use and how to use them is critically important. Today Iâm going to discuss all the options for the treatment of acute agitation in clinical practice.
What is Agitation?
Agitation is an extreme form of arousal that is associated with increased verbal and motor activity that poses a threat to themselves and others. Agitation needs to be recognized immediately and addressed due to the risk of harm to the patient and others.
Verbal De-escalation is Always The First Step
Engaging the patient and attempting to elicit a reason for the agitation should always be attempted first. In many cases patients are hungry, tired, or overly stimulated by the busy inpatient or ED setting. If these interventions are unsuccessful and the patient remains agitated security staff lead by the physician should inform the patient that if the behavior continues medication will be administered for safety purposes.
Thinking About Medication
Sometimes using medication is unavoidable and is required to facilitate a medical evaluation. We need to be mindful of the potential adverse events associated with sedating medication. The most common adverse effects are hypoxia, airway obstruction, QTc prolongation, bradycardia, and hypotension. Patients over the age of 65, alcohol intoxication, and multiple medication administrations in a short period of time increases the risk of adverse events.
Routes of Administration
Itâs always best to offer PO (oral) medication prior to using IM or IV medications. In the inpatient setting we do not allow IVs due to the potential risk of self-harm; IM medication is second route of administration commonly used. I will usually use risperidone 2 mg or olanzapine zydis 10 mg because it begins dissolving immediately once the person puts it in their mouth in both cases. Oral medications can be âcheekedâ and will also take longer to start working. In general, itâs important to note the onset of PO medication will be slower. Antipsychotic medications and benzodiazepines are commonly used for sedation in acute agitation.
First Generation Dopamine Blocking Medications
These medications have been around for a long time and have a good safety profile when used to treat acute agitation. Some antipsychotics have the risk for more side effects due to their ability to lower seizure threshold, cause hypotension, and have an increased anticholinergic burden.
Haloperidol
This is the go-to antipsychotic for acute agitation. It works by blocking D2 receptors and can be given PO, IM, or IV. Typical dosing is 2.5 to 10 mg with a recommended maximum dose of 20 mg/day. The average time to sedation is 25-28 minutes and the mean total time sedated is 84-126 minutes. The main risk for haloperidol is EPS such as acute dystonic reactions. To avoid this situation, we usually combine Haldol with lorazepam or benztropine/diphenhydramine. Haldol is also well studied and relatively staff for those who are acutely intoxicated with alcohol.
Chlorpromazine
I will usually go to chlorpromazine when I need someone to sleep such as cases of mania with acute agitation. I find it to be a little more sedating and it can be combined with diphenhydramine. Doses can range from 25 mg to 200 mg depending on the level of severity. The maximum dose is 400 mg/day.
Second Generation Dopamine Blocking Medication
Second generation medications have the added advantage of lower risk for QTc prolongation, less sedation, and fewer extrapyramidal symptoms compared to the first-generation options.
Olanzapine
Olanzapine comes in PO, IM, and IV forms, and the typical starting dose is 10 mg. Olanzapine reaches peak concentration in 15-45 minutes and its half-life is 2-4 hours. The incidence of EPS is much lower than injectable haloperidol. There is very rare incidence of QTc prolongation. There is some evidence that 10 mg of olanzapine is more effective than 5 mg of haloperidol for sedation and that most patients are adequately sedated at 15 minutes after administration of 10 mg olanzapine compared to 5 mg and 10 mg of haloperidol.
It’s important to note that multiple studies have demonstrated adverse events when olanzapine is combined with benzodiazepines. Although the risk may be overstated itâs best to avoid this combination unless necessary. Olanzapine is highly anticholinergic and should be avoided in cases where anticholinergic overdose is suspected.
Ziprasidone
Ziprasidone is a second-generation medication that is available in either PO or IM formulations. The PO form of the medication has little utility in acute agitation, but the IM version can be useful. Time to onset of effect is usually 15-20 minutes and it reaches peak concentrations in 30-45 minutes. The duration of sedation is at least 4 hours. Ziprasidone carriers the highest risk of second-generation medications for QTc prolongation
Risperidone
Data for risperidone in acute agitation is limitted. It does have the advantage of coming as an oral disintegrating tablet. In most cases I would administer 2-4 mg depending on the severity of symptoms. It can be a good option for patients with psychotic agitation due to paranoid delusions. Itâs a good option for elderly patients and pregnant patients who can take PO medication.
Benzodiazepines
Benzodiazepines are another good choice when it comes to rapid treatment of acute agitation. Benzodiazepines do carry the risk of creating a paradoxical reaction in the elderly, but itâs relatively rare and seen in only 1% of cases. Flumazenil (benzodiazepine blocker) can be used to counteract this paradoxical reaction if needed. There is risk for respiratory depression especially in those who are already on central nervous system depressants. If withdrawal is suspected from benzodiazepines or alcohol, this is the first line option for treatment.
Lorazepam
Lorazepam is available in IV, IM, and PO formulations. The typical dosing is 0.5-2 mg IM or PO. This medication can be given every 30 minutes up to a maximum dose of 12 mg/day. Lorazepam is longer acting than midazolam and has an average time to adequate sedation of 32 minutes.
Midazolam
Midazolam is available in IM formulation and the typical dosing begins at 2-5 mg. The average time to sedation is 13-18 minutes for the IM formulation. When given IM the total time of sedation is between 82-105 minutes. Midazolam offers the advantage over lorazepam because itâs onset of action is faster. Midazolam also works faster than haloperidol or ziprasidone. The duration of sedation is also shorter.
Medication Combinations
In most cases these medications will be used in combination to maximize their effects. The most well-known is the so called B52 which consists of Haloperidol 5 mg, Lorazepam 2 mg, and diphenhydramine 50 mg. The idea here being 50, 5, and 2 are the doses and B52 because itâs like the B52 bombers when it comes to sedation. I also often combine chlorpromazine and olanzapine with 50 mg of diphenhydramine in the IM formulations. For PO risperidone you can combine it with PO lorazepam and diphenhydramine if needed. With ziprasidone I will usually give this one alone without lorazepam or diphenhydramine.
Physical Restraints
The utilization of physical restraints may be necessary when safety is a major concern. In some cases, verbal de-escalation, and medication are not enough. The problem is physical restraints can lead to injury for both the patient and staff. Patients who continue to fight against the restraints can have a complication known as rhabdomyolysis where the muscles are literally breaking down from the person fighting against the restraints. Sedation should always be provided when physical restraints are used. What happens if a person is given high doses of sedating medications and placed in psychical restraints but remains agitated?
Special Cases
Itâs rare but I have had two clinical scenarios where an individual was placed in restraints given multiple doses of medications and remained severely agitated. Due to concern for the patientâs safety and risk of rhabdomyolysis I had to transfer each of these cases to the medical floor for IV dexmedetomidine (Precedex) which is commonly used to sedate patients in the intensive care unit who are intubated. After a short course of Precedex treatment each patientâs agitation resolved. There is now a rapidly dissolving film of dexmedetomidine available for acute agitation in bipolar disorder and schizophrenia, so I guess I was ahead of the times when I made these clinical decisions.
Conclusion
Agitation is a complicated and multifactorial process that requires quick action. To maintain safety, agitation needs to be quickly identified and managed. Verbal de-escalation and comfort measures should always be the starting point. If medications are required there are several individual and combinations that can be selected based on the clinical situation. When all else fails physical restraints remain a possibility until medications have had time to reach peak concentrations and effectiveness.
Stage 1: more than one adequate trial of 1 major class of antidepressants
Stage 2: Failure of more than 2 adequate trials of two different classes of antidepressants
Stage 3: stage 2 + TCA
Stage 4: Stage 3 + MAOI
Stage 5: Stage 4 + bilateral ECT
With every medication or neuromodulation procedure used that doesnât work, the more treatment resistant the depression becomes.Â
Antidepressant Response RatesÂ
Frist Medication Trial: 50% respond and 37% have remission
Second Medication Trial: Another 29% respond and 31% have remission
Third Medication Trial: 17% respond and 14% have remission
Fourth Medication Trial: 16% respond and 13% have remission
The overall cumulative remission rates are 67%, keeping in mind that people who progressed through more treatment stages had higher relapse rates and more residual symptoms including anhedonia, emotional blunting, and lack of motivation.
If someone is having a poor response to medication, what do you do?
We know that bipolar disorder is missed in a significant number of patients who present with depression about one in five will be misdiagnosed. We also know that antidepressants can be mood destabilizing in bipolar illness resulting in mixed features and rapid cycling. Other things that can interfere with response include substance use disorder, personality traits, and PTSD.Â
Medical Comorbidities that can interfere with antidepressant response include hypothyroidism, Cushing disease, Parkinsonâs disease, cancer, vitamin/nutritional deficiencies, and viral infectionsÂ
Psychosocial factors that contribute to treatment resistanceÂ
-Female sex
-Older Age
-Single Unmarried (happiness studies indicate that good relationships are very important)
-UnemploymentÂ
Symptoms that make TRD more LikelyÂ
-Recurrent episodes usually 3 or more
-Severe depression and inpatient admission
-Anxiety, Insomnia, or MigraineÂ
When Your First Choice Fails
There are several approaches
-Switch antidepressant classes
-Combine antidepressants
-Add a dopamine blocking medication
-Add L-methylfolate
-Add Psychotherapy
-Start NeuromodulationÂ
Whatâs the most effective strategy
Hands down the most effective thing to do if a patient has a poor response to the initial antidepressant treatment is to add a dopamine blocking medication. Response and remission rates are much higher, but it comes at the price of increased side effect potential.Â
What are the most used Dopamine Blockers in Antidepressant Augmentation
-Quetiapine
-Olanzapine
-Risperidone
-Aripiprazole
-Ziprasidone
Older patients 65 years and older respond better to aripiprazole augmentation than switch to bupropion, or combination with bupropion.
Brexpiprazole: 1-3 mg/day Adjunctive for DepressionÂ
Most Common Concerns patients have about being on dopamine Blocking MedicationÂ
-Weight gain 60% of people report this concern
-Metabolic side effects
-EPS
-Sedation
-Akathisia
-Prolactin-related EffectsÂ
Anti-Inflammatory MedicationsÂ
For those with elevated inflammatory biomarkers specifically c-reactive protein there is some emerging evidence that these treatments work.
-Medications like Celecoxib, Omega-3 fatty acids, statin drugs and minocycline
-Weight loss
-Effect Size: 0.55
-Higher response and remission rates
-May only work in those with high inflammatory biomarkersÂ
Glutamate ModulatorsÂ
-Ketamine Infusions and Esketamine: both work and a reasonable option if TRD
-There are several medications in developmentÂ
Psychotherapy in TRD
Unfortunately, what we find with TRD is psychotherapy does not prevent TRD, it doesnât mean there is no benefit it just means future episodes will not be prevented by psychotherapy. On its own, psychotherapy may not be as helpful as we would like in TRD but when combined with medication it does help. That tells us about the importance of evaluating severity of depressive episode.
