Psychiatric emergencies: Pathology review
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A 53 year old male named Noah is brought to the emergency department by his son, who found him with an empty bottle of fluoxetine in his hand. His son mentions that Noah was recently diagnosed with depressive disorder. Upon physical examination, you realize that Noah has a body temperature of 38.9 degrees Celsius, or 102.02 degrees Fahrenheit, and a blood pressure of 162 over 95 millimeters of mercury. In addition, Noah’s pupils appear dilated, and his muscles are very stiff. Finally, neurological examination reveals that Noah has overactive reflexes. Later that day, a 34 year old female named Amelia is brought to the emergency department by her husband. He explains that Amelia has a medical history of schizophrenia, and a few days back she took multiple doses of haloperidol. Upon physical examination, Amelia’s body temperature is 38.7 degrees Celsius or 101.66 degrees Fahrenheit, and her blood pressure is 170 over 100 millimeters of mercury. Similarly to Noah, Amelia has muscle stiffness, but neurological examination reveals diminished reflexes.
All right, now, both Noah and Amelia seem to have some form of psychiatric emergency, which is when a psychiatric condition becomes life-threatening and requires prompt treatment. For your exams, some high yield psychiatric emergencies include suicide attempts, serotonin syndrome, acute dystonia, neuroleptic malignant syndrome, tyramine-induced hypertensive crisis, and delirium tremens.
Now, a very relevant psychiatric emergency, not only for your exams, are suicide attempts. Suicide is when someone takes their own life intentionally. Now, many suicide attempts can be prevented by keeping an eye out for red flags or risk factors, which can be easily remembered with the memory trick SAD PERSONS. The first S here stands for sex, as suicide tends to be more common among males. Next, A stands for age, so remember that suicide is more common among young adults and the elderly. For your exams, you should know that suicide is the second leading cause of death among individuals aged 15 to 34 in the USA, behind motor vehicle crashes. D is for depressive disorder, which is a psychiatric disorder that causes a persistent feeling of sadness, associated with a loss of interest in everyday activities like hobbies. Then P stands for previous suicide attempts, which remember is the most important risk factor for suicide. E stands for excessive alcohol or substance abuse, which causes individuals to be more impulsive, taking risks they normally wouldn’t take like driving recklessly. Oftentimes, alcohol or substance abuse occur together with depression. In fact, many people who experience depression turn to alcohol or substances to temporarily numb their feelings. And vice versa, chronic alcohol or substance abuse can ultimately cause depression, creating a vicious cycle. R is for rational thinking loss in psychosis, a severe mental disorder that can impair thought and emotions, to the point where individuals lose touch with reality. The next S is for sickness, which refers to chronic nonpsychiatric diseases, like end-stage cancer, that can be very hard to deal with. O stands for organized plan, which is when the individual has a specific method for suicide in mind. What’s very important to remember is that the most common method involves firearms like guns. For that reason, it’s key to evaluate if the individual has access to firearms. Next, N stands for no social support, meaning that they have no friends or family to turn to during vulnerable times. The last S refers to stated future intent, which is when a person expresses their suicidal thoughts or intentions.
Now, even if there are no risk factors for suicide, some people may impulsively take their lives in a moment of overwhelming life stress. This could be due to the loss of a loved one, going through a financial crisis, or experiencing various social pressures. Because of that, it’s just as important to focus on protective factors that can reduce the potential for suicidal behavior. Protective factors can include helping individuals develop self-esteem and coping skills. In addition, having cultural and religious beliefs, as well as a sense of purpose in life can discourage suicide. Finally, a key protective factor is companionship and emotional support.
If you suspect that someone’s at risk for attempting suicide, the first thing you should do is evaluate how serious the threat is, and suggest that they seek for help or be hospitalized voluntarily. If they refuse to get help, and they’re an imminent threat, they should be hospitalized involuntarily.
The next high yield psychiatric emergency is serotonin syndrome. Now, serotonin, also called 5-hydroxytryptamine or 5-HT for short, is a neurotransmitter that mainly helps regulate mood and emotions. Presynaptic serotonergic neurons synthesize serotonin and store it in small vesicles. When an action potential reaches the presynaptic membrane, the vesicles fuse with the membrane and release the serotonin into the synaptic cleft. The free serotonin then binds to serotonin or 5HT receptors on the postsynaptic neuron, causing it to fire off its own action potential. The presynaptic membrane also has serotonin reuptake transporters or SERTs, which take serotonin back into the presynaptic neuron, so the postsynaptic neuron stops firing. Inside the presynaptic neuron, some of this serotonin is packed into pre-existing vesicles, waiting to be released once more, while the rest of the serotonin is broken down by mitochondrial enzymes called monoamine oxidases or MAOs for short.
Okay, now, serotonin syndrome is a potentially life-threatening condition caused by high levels of serotonin in the brain. For your tests, remember that most cases of serotonin syndrome occur in people taking psychiatric medications to treat depression, which can be classified as typical and atypical antidepressants. Typical antidepressants include medications that block serotonin reuptake transporters, such as selective serotonin reuptake inhibitors or SSRIs like fluoxetine, serotonin norepinephrine reuptake inhibitors or SNRIs like duloxetine, and tricyclic antidepressants or TCAs like amitriptyline. Typical antidepressants also include medications called monoamine oxidase inhibitors or MAOIs for short, which inhibit the breakdown of serotonin by monoamine oxidases. What’s very high yield is that serotonin syndrome is most likely to occur when MAOIs are taken in combination with another antidepressant medication! Now, some atypical antidepressants, such as vilazodone and vortioxetine, can also cause serotonin syndrome by blocking serotonin reuptake inhibitors. Another important psychiatric medication that can cause serotonin syndrome is buspirone, which is mainly used to treat anxiety disorders. What buspirone does is it binds to serotonin receptors on the postsynaptic membrane and activates them, thereby potentiating the effect of serotonin in the central nervous system.
Now, it’s important to note that serotonin syndrome can also be caused by some nonpsychiatric medications, which you can remember using the mnemonic: The LOSt MD Took MDMA - Tramadol, Linezolid, Ondansetron, St. John’s wort, Meperidine, Dextromethorphan, Triptans, and MDMA. Okay, so tramadol, meperidine, dextromethorphan, and St. John’s wort, all increase the concentration of serotonin by blocking serotonin reuptake transporters. Another medication you should think of is linezolid, which blocks monoamine oxidases and prevents them from breaking down serotonin. Next we have ondansetron, which acts as a serotonin receptor antagonist, which means that it binds and inhibits serotonin receptors on the postsynaptic membrane. As a result, serotonin can’t bind to its receptors, so it builds up throughout the central nervous system. On the flip side, triptans act as serotonin receptor agonists, so they bind and activate serotonin receptors. Finally, MDMA stimulates the presynaptic neurons to release serotonin.
Okay, to remember the most common clinical features of serotonin syndrome, think of the 3 A’s, which are autonomic effects, abnormal neuromuscular activity, and altered mental status. Autonomic effects can include gastrointestinal disturbances like diarrhea, diaphoresis or excessive sweating, mydriasis or dilated pupils, and hyperthermia or increased body temperature, as well as hypertension or elevated blood pressure, and tachycardia or increased heart rate. Abnormal neuromuscular activity may manifest as myoclonus or muscle twitching, hyperreflexia or excessive reflexes, hypertonia or increased muscle tone, tremor or involuntary shaking, and even seizures. Finally, altered mental status may present with agitation, confusion, hallucinations, or even coma.
Treatment of serotonin syndrome involves the administration of benzodiazepines and supportive care, and in severe cases administration of cyproheptadine, which can inhibit serotonin receptors.
Now, another very similar psychiatric emergency is neuroleptic malignant syndrome. Now, the exact mechanism behind neuroleptic malignant syndrome is unclear, but it seems to be associated with dopamine receptor blockade. In fact, it typically occurs in individuals taking antipsychotic medications, which remember is often used to treat schizophrenia. Most cases are caused by typical antipsychotic medications, such as haloperidol. Now, typical antipsychotics work by blocking dopamine D2 receptors, which are found in various pathways within the brain. Some high yield pathways include the mesolimbic pathway, which controls feelings of motivation, reward, and desire; the mesocortical pathway, which helps regulate emotions; and the nigrostriatal pathway, which helps control involuntary movements and coordination. Less frequently, neuroleptic malignant syndrome may be caused by atypical antipsychotics like clozapine, which can block both dopamine D2 receptors and serotonin receptors. What’s really important to note is that medications are usually not enough to develop neuroleptic malignant syndrome. In fact, there seems to be a genetic predisposition in those who have genetic variations in the gene that codes dopamine D2 receptors. And that’s a high yield fact!
Symptoms of neuroleptic malignant syndrome typically start days to weeks after starting the medications. To help you recall the most high yield symptoms, think of FEVER. F actually stands for fever or hyperthermia, and it’s one of the most characteristic symptoms of neuroleptic malignant syndrome. The first E stands for encephalopathy or brain dysfunction, which presents with an altered mental status that can range from confusion or delirium to coma. Then there’s V for vitals, which are typically unstable. This means that individuals with neuroleptic malignant syndrome may experience tachycardia, as well as a labile blood pressure that may suddenly go from normal to really high levels. Now, unstable vitals can often be associated with diaphoresis, and that’s a very high yield fact! Okay, the second E stands for enzymes, such as creatine kinase that may be elevated in blood, as well as myoglobinuria or the presence of myoglobin in urine. What’s important to note here is that these enzymes are normally found inside skeletal muscle cells, so finding them around in blood or urine typically indicates rhabdomyolysis or abnormal skeletal muscle breakdown. And what's even more important is that these enzymes can be harmful to the kidneys and often lead to acute renal failure. Finally, R stands for rigidity of muscles, which is characterized by an increased muscle tone that causes constant resistance when another person tries to move the joint of the affected individual. In a test question, this may be referred to as “lead pipe” rigidity.
Now, some of these symptoms may trick you into thinking of serotonin syndrome, so to set these two apart, remember that neuroleptic malignant syndrome tends to cause more severe hyperthermia and muscle rigidity. In addition, individuals with serotonin syndrome typically also experience mydriasis, hyperreflexia, myoclonus, and diarrhea. So be sure to keep an eye out for these clues!
Sources
- "Robbins Basic Pathology" Elsevier (2017)
- "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
- "Pathophysiology of Disease: An Introduction to Clinical Medicine 8E" McGraw-Hill Education / Medical (2018)
- "Diagnostic and Statistical Manual of Mental Disorders" NA (1980)
- "Suicide prevention strategies revisited: 10-year systematic review" The Lancet Psychiatry (2016)
- "Psychiatric Emergencies in the Intensive Care Unit" AACN Advanced Critical Care (2015)
- "Neuroleptic Malignant Syndrome" American Journal of Psychiatry (2007)