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Neuroleptic Malignant Syndrome

by Helen Farrell, MD
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    00:00 Now, neuroleptic malignant syndrome is a very noteworthy side effect coming from antipsychotics.

    00:07 So this is life-threatening. It’s characterized by a fever, altered mental status, muscle rigidity, and autonomic dysfunction.

    00:16 This often can occur on exams, so let’s take a moment to talk about it.

    00:20 It’s more common in males. In fact, probably most common in young African American males in their 20s.

    00:27 Although it’s a significant side effect, thank goodness, it is rare but still important to know about, especially on exams.

    00:34 And it’s a true medical emergency that can in fact lead to death.

    00:39 So in your assessment, what you’re going to look for when determining whether or not somebody has neuroleptic malignant syndrome.

    00:46 Well, before they actually will develop the syndrome, it’s usually preceded by the patient being in a catatonic state.

    00:54 Then they’ll develop a fever, instability like tachycardia, blood pressure changes, and they'll be sweating profusely.

    01:02 They may have a leukocytosis, a tremor, elevated CPK, and also rigidity.

    01:09 Fever and rigidity are really the two hallmarks of NMS that you want to be looking for.

    01:14 So they may also have muscle spasms, trouble swallowing.

    01:19 They may have some parkinsonian symptoms, and sustained motion or restlessness.

    01:25 They may have uncontrollable repetitive movements.

    01:29 We already mentioned the fever, rigidity, unstable vital signs. And you’re looking for blood work that shows a high CPK, high potassium, and elevated white blood cells. The differential diagnosis of the neuroleptic malignant syndrome includes meningitis, encephalitis, drugs induced condition and heat strokes.

    01:46 If you have to treat a NMS patient, the first thing is the stop the offending agent.

    01:51 You also have to admit to ICU and put supportive measures like IV hydration and fluids.

    01:56 Dantrolene should be used and also agents like bromocriptime, benzodiazepines or amantadine.

    02:02 Lastly, ECT or electroconvulsive therapy can also be used in selective cases.

    02:09 Something important to note is that unlike what many people think, NMS is not actually an allergy to a medication.

    02:16 It’s a very adverse and bad reaction, but it doesn’t mean that somebody can never take an antipsychotic again or try different antipsychotic later.

    02:25 You simply want to treat the emergency, let the patient stabilize, and it’s actually okay to slowly introduce an antipsychotic in the future. So NMS is not an allergy.

    02:37 The mechanism of action now for atypical antipsychotics.

    02:40 So now, we’re moving into discussing the newer forms of neuroleptics. They are called atypicals.

    02:46 So these have some affinity for dopamine receptors but far more affinity for other neurotransmitters.

    02:53 Things like serotonin receptors, histamine receptors, and alpha receptors.

    02:58 And so therefore, they have a very different side effect profile.

    03:01 And remember, these are very useful in the treatment of negative symptoms of psychosis.

    03:07 Some examples of atypical antipsychotics include here clozapine, risperidone, quetiapine, olanzapine, and ziprasidone.

    03:16 There are, of course, many more and newer ones are on the market all the time.

    03:21 And you’re looking out for side effects from your patient who can incur any of the following.

    03:26 So when it comes to clozapine, this is a very notable atypical antipsychotic.

    03:33 So it’s actually one of the oldest atypical antipsychotics, the oldest atypical.

    03:38 And it’s not used quite as frequently despite it being around for so long.

    03:45 And that’s because it has a number of potentially deadly side effects that require very intense monitoring.

    03:50 Having said that, you must know that clozapine is a great medication to use in the patient who is described as being treatment resistant in terms of their psychosis.

    04:02 So although it’s usually a later resort and sometimes a last resort, it really is effective in treating treatment resistant psychosis.

    04:10 Now, it’s notable that there’s a 1% incidence of agranulocytosis with this, and a 2 to 5% incident of seizures with clozapine.

    04:20 So as I mentioned before, there are notable side effects.

    04:23 The one that tends to come up most commonly on board exams is that side effect of agranulocytosis.

    04:31 So another atypical antipsychotic is olanzapine.

    04:36 And a little pearl to note about this is that it actually can cause significant weight gain, as well as hyperlipidemia, glucose intolerance, and therefore, can lead to diabetes in patients.

    04:49 So, let’s go through some of them in more detail.

    04:51 So here are some of the atypical antipsychotics, and you can read here that we’ve got their features and potential side effects.

    04:58 I mentioned with olanzapine the potential for weight gain.

    05:02 And one of the things that’s notable about quetiapine is that not only is it indicated for psychosis, but this can actually be used as well as a good antidepressant and mood stabilizer in patients who have had a lot of depression.

    05:17 A notable thing about risperidone is that it actually comes in an injectable form, a long-acting injectable form for that patient who may not be so compliant with medication.

    05:28 Olanzapine and ziprasidone, on the other hand, have short-acting injectable options.

    05:34 So these are good for emergent situations on an inpatient unit or in an emergency room.

    05:39 However, these medications can disrupt the QTc interval, especially ziprasidone.

    05:46 So remember to check in EKG as a baseline before starting your patient on this.

    05:51 I talked a little bit about clozapine before and the importance of knowing about its side effect, agranulocytosis.

    05:58 There are a lot of other side effects that can cause too though. It’s extremely a weight gaining medication.

    06:05 So, weight gain is important and it can lead to something like diabetes and the metabolic syndrome, which needs to be monitored for.

    06:13 It can also cause myocarditis and sialorrhea where patients may describe waking up in a pool of their own saliva.

    06:21 So these are other things.

    06:22 And a neat little trick for treating the sialorrhea is to actually give a patient atropine drops at night, on their tongue.

    06:31 Now, a constellation of symptoms that are associated with the atypical antipsychotics are of course the metabolic syndrome.

    06:39 And the symptoms here include elevated fasting glucose, hypertension, abdominal obesity, elevated triglycerides, and a decrease in HDL cholesterol.

    06:50 Things that really need to be monitored for closely when you’ve got a patient on an atypical antipsychotic.

    06:57 Here’s a quiz for you. Which two atypical antipsychotics are most commonly associated with the metabolic syndrome? So we talked about these earlier.

    07:07 There are two atypicals that are really known for causing profound weight gain.

    07:11 Right, it’s clozapine and olanzapine.

    07:15 Now, how would you treat the metabolic syndrome? Well, you actually want to really encourage your patient to get on a weight reduction program, maybe exercising 30 minutes a day, if tolerated.

    07:27 Also, making healthy dietary changes, probably get a nutritional consult for your patient.

    07:31 And then you may also consider reducing the dose of their medication or switching them to another agent that might be a little bit more weight neutral.

    07:40 So in terms of further going through our atypical antipsychotics, I want to bring back in the important point of noting that some medications are available as injectable forms.

    07:56 This is a really important point because as I mentioned, some patients maybe not tolerate medicine or not comply with it, and others may just opt to not take a pill every day. So, both atypical and typical is alike come in injectable forms.

    08:13 So in terms of long-acting forms, fluphenazine, which is of course a typical medication, as is haloperidol, are available in long-acting injections, and so is risperidone. Some newer agents include paliperidone.

    08:27 This is an atypical agent that’s newer and comes in a monthly injection, as does aripiprazole.

    08:34 Now, not only do paliperidone and aripiprazole come in long-acting injectables, they’re also available in short-acting injectables for those emergent situations.

    08:45 So we talked about a couple of them, but overall, do you know of any other antipsychotics that can be used emergently in short-acting injectable form? Well, fluphenazine, haloperidol, chlorpromazine, aripiprazole, ziprasidone, and olanzapine are few examples.

    09:03 To go back to clozapine, a very important medication to know about for your boards because it can cause agranulocytosis, which is very important to remember.

    09:14 It requires strict blood monitoring.

    09:16 And so when monitoring blood counts for patients who are on clozapine, when should you actually discontinue clozapine? So, when are the blood counts so bad that you have to stop the medication? Well, it’s when the white blood cell count drops to below 2.000 or 3.000, or the absolute neutrophil count falls below 1.500. Patients should be monitored if this happens.

    09:43 Now, the typical monitoring schedule for clozapine includes weekly white blood cell counts and absolute neutrophil counts every week for the first six months of treatment.

    09:54 If somebody has done fine on the medication for six months, you can then taper back to checking their white blood cell count and ANC twice a month for six months.

    10:06 If they do fine with that, then for the rest of their treatment, they need to be checked monthly.

    10:13 So, what are the recommendations? And so I just went over this and here’s a slide to point out the baseline check and then the frequency of checking WBC and ANC.

    10:25 And again, you’re looking for it to remain for the white blood cell count above 3.500 and you’re looking for the ANC to remain above 1.500 to know that your patient is safe to continue with the medication at least in terms of evading agranulocytosis.

    10:40 Other therapies that can be helpful to your patient include non-pharmacological approaches.

    10:46 So, think about behavioral treatment, things like social skills, self-sufficiency training, and how to act appropriately in public.

    10:53 This can all be fostered through both individual psychotherapy and group therapy.

    10:59 So I want to ask you though, what cognitive problems can be seen in schizophrenia? Well, sometimes there is a deficit in processing complex information, maintaining a steady focus, working memory, or distinguishing between relevant and irrelevant stimuli, as well as abstract thinking.

    11:17 So, these are good things to keep in mind when dealing with the patient with schizophrenia.

    11:21 And there can be limitations in terms of training someone.

    11:25 Sometimes it’s difficult to generalize what they learn in a group or a classroom to the real world setting.

    11:33 So how can you, as the therapist, best help your patient with schizophrenia? We’ll be direct and straightforward and take an active and assertive posture to treatment.

    11:43 So we’ve summarized now the pharmacotherapy of antipsychotics, giving you some of the highlights, keeping in mind when these medications are indicated and useful, and definitely, keep in mind the side effect profile as you’re studying for your boards.


    About the Lecture

    The lecture Neuroleptic Malignant Syndrome by Helen Farrell, MD is from the course Major Psychiatric Disorders.


    Included Quiz Questions

    1. It is a life-threatening reaction to tricyclic antidepressants.
    2. Autonomic dysfunction is often seen including diaphoresis, tachycardia and tachypnea.
    3. The patient can have altered mental status.
    4. It is more common in African American males.
    5. Hyperthermia often beyond 38 °C/100.4 °F and severe muscular rigidity are seen.
    1. IV fluids, cooling and Dantrolene.
    2. Dantrolene, Benzodiazepines and heating pads.
    3. IV fluids, anticholinergics and high potency D2 blockers.
    4. β-blockers, cooling and Cholinergic agents.
    5. IV fluids, high potency D2 blockers and β-blockers.
    1. Agranulocytosis
    2. Aplastic anemia
    3. Hyperemesis
    4. Thrombocytopenia
    5. Erythrocytosis
    1. Quetiapine
    2. Olanzapine
    3. Risperidone
    4. Clozapine
    5. Ziprasidone
    1. Aripiprazole
    2. Risperidone
    3. Ziprasidone
    4. Clozapine
    5. Haloperidol
    1. Discontinue treatment when the absolute neutrophil count (ANC) is >1500.
    2. Clozapine is the most common atypical agent causing metabolic syndrome.
    3. There is a 2-5% incidence of seizures.
    4. We can continue the treatment if the WBC count is >3500.
    5. Weekly WBC and ANC checks.

    Author of lecture Neuroleptic Malignant Syndrome

     Helen Farrell, MD

    Helen Farrell, MD


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