Antipsychotics + Akathisia

[seminoma]

Patient is started on aripiprazole and develops akathisia. You lower the dose to the minimum, but his akathisia does not improve. What do you do now?

A. Add benztropine
B. Add diphenhydramine
C. Add propranolol
D. Add lorazepam
E. Discontinue aripiprazole and start a different antipsychotic

Correct answer is (highlight): C

Explanation below.


This is a question from Lange Psychiatry. The explanation says benztropine is used for dystonias and parkinson-like symptoms and that diphenhydramine is used for acute dystonia, but is ineffective in treating atypical antipsychotic-induced akathisia. FA has benztropine and diphenhydramine listed as treatment for antipsychotic-induced EPS. I remember learning in class that beta blockers can be used for akathisia (and for actual tremor), but I didn't know that benztropine/diphenhydramine are not used for akathisia. Has anyone come across something in a more reliable resource (Uworld...?) that agrees with this explanation from Lange?

---

Members don't see this ad.

 

[Apoplexy__]

I can't think of a source off the top of my head, but every resource I've seen says to treat akathisia with propranolol.

It seems your question is why benztropine and diphenhydramine can't be used in akathisia -- can't help you with that.

 

[seminoma]

I can't think of a source off the top of my head, but every resource I've seen says to treat akathisia with propranolol.

It seems your question is why benztropine and diphenhydramine can't be used in akathisia -- can't help you with that.

Ok thanks. I'm also curious how to interpret the FA section on page 517.

Extrapyramidal system side effects (e.g., dyskinesias). Treatment: benztropine or diphenhydramine.

So ONLY dyskinesias respond to benztropine/diphenhydramine? There's no mention of propranolol for akathisia in FA, but I'll go with it.

 

[Apoplexy__]

Ok thanks. I'm also curious how to interpret the FA section on page 517.

So ONLY dyskinesias respond to benztropine/diphenhydramine? There's no mention of propranolol for akathisia in FA, but I'll go with it.

Yeah, I see what you mean. I'm really surprised FA doesn't address the issue. My subscription for Step 1 UWorld ran out (I'm MS3) but here's an excerpt from one of a couple questions from UWorld Step 2 that say you use propanolol for akathisia:
"Beta-blockers such as propanolol are used to treat akathisia, a type of EPS that can occur at any time during the course of antipsychotic use."

Honestly, I picked it up from Firecracker as an MS2, saw it in a couple other sources along the way including in Step 2/shelf resources, and never saw anything that contradicted it. I'm not sure if you can use benztropine/diphenhydramine for akathisia as well, as a brief review of my available materials didn't say you couldn't.

Here's just how I memorized things for Step 1:
Acute dystonia: Benztropine/diphenhydramine
Akathisia: Propanolol
Parkinsonian symptoms: Benztropine/diphenhydramine
Tardive dyskinesia: Cessation of traditional antipsychotic --> Switch to atypical antipsychotic

 

[seminoma]

Yeah, I see what you mean. I'm really surprised FA doesn't address the issue. My subscription for Step 1 UWorld ran out (I'm MS3) but here's an excerpt from one of a couple questions from UWorld Step 2 that say you use propanolol for akathisia:
"Beta-blockers such as propanolol are used to treat akathisia, a type of EPS that can occur at any time during the course of antipsychotic use."

Honestly, I picked it up from Firecracker as an MS2, saw it in a couple other sources along the way including in Step 2/shelf resources, and never saw anything that contradicted it. I'm not sure if you can use benztropine/diphenhydramine for akathisia as well, as a brief review of my available materials didn't say you couldn't.

Here's just how I memorized things for Step 1:
Acute dystonia: Benztropine/diphenhydramine
Akathisia: Propanolol
Parkinsonian symptoms: Benztropine/diphenhydramine
Tardive dyskinesia: Cessation of traditional antipsychotic --> Switch to atypical antipsychotic

Big help man, thanks a lot. How are you liking FC for Step 2 (pm me if it's easier)? I bit the bullet and bought a subscription through next October (didn't want to, but it was cheaper than just paying full price through May). I've been using it since MS1.

 

[Apoplexy__]

Sure thing. I gotta update that dedicated thread I made for FC Step 2, but in short, I haven't been using it. For the few shelfs I've taken, I haven't even been able to complete the "gold standard" resources for that shelf. So for me using FC for Step 2 right now, it's a bit like using FC Step 1 while sacrificing either UWorld, Pathoma, or First Aid.

Also, the quality still isn't there -- you still have to rely on the weekly blog for quality topics. As of right now, any time I've been tempted to use it a bit for a shelf, only half or so of the topics of that subject were in the list of topics updated to standards as seen in the blog. The current plan is to have everything up to standards by 2015.

My current expectation is that I might try and sneak in some work on it during rotations that don't have shelf exams. Even then though, it's a trade-off for other things (e.g. review FA 2014, research, or start preparing for the shelf for the next rotation).

 

[Transposony]

Among all EPS, akathisia is unique in that it can occur at any time and does not respond to typical treatment with benztropine and diphenhydramine.
Although the mechanism is not known but it is suggested that CNS pathways outside the nigrostriatal pathway are involved based on the fact that it does happen with aripiprazole (which is partial D2 agonist) and quetiapine (which has a very weak D2 affinity).
Other effective treatment for akathisia is clonazepam in addition to propanolol both of which are ineffective for other forms of EPS.

 

[voicesinmyhead]

why does one get akathisia with anti depressants like Sertraline?

 

[Mr. Mojo Risin]

why does one get akathisia with anti depressants like Sertraline?

It has been suggested that inhibitory input from the serotonergic raphe nuclei to the subtantia nigra may be one mechanism by which SSRIs can induce akathisia and other movement disorders.

Here is an excerpt from an article that discusses this interaction. It also mentions that noradernergic mechanisms may also be involved, confirming the propranolol answer:

http://www.psychiatrictimes.com/articles/movement-disturbances-associated-ssris

"Serotonin (5-HT)-containing raphe nuclei extend diffuse interconnections to the DA-rich substantia nigra (Dray, 1981). Neurophysiologic and electric stimulation studies demonstrated that the 5-HT released by the raphe nuclei inhibit striatal neurons, an effect which is reversed by 5-HT antagonists (Davies and Tongroach, 1978). Thus, it is plausible that inhibitors of neuronal 5-HT reuptake, by increasing the availability of 5-HT, might be expected to produce an effect similar to that of DA-blocking agents (Figure). In fact, high doses of fluoxetine (Prozac) have been shown to inhibit DA synthesis in the forebrain, hippocampus and portions of the basal ganglia, specifically the caudate-putamen (Baldessarini and Marsh, 1990). Hence, it can be expected that movement disturbances might arise from SSRI use.

The physiologic processes underlying the development of akathisia may involve the interaction of serotonergic and DA pathways innervating mesolimbic systems. While not depicted here, it is suggested that the inhibitory input to these DA pathways produces the overt and covert restlessness characteristic of akathisia. Noradrenergic mechanisms may also be involved.

The mechanisms underlying SSRI-induced movement disorders are likely to be more complex than has been suggested above. A few case reports suggest improvement of parkinsonism and dystonia with the addition of SSRIs (Durif et al., 1995; Keppel Hesselink, 1993; Meerwaldt, 1986). It is possible that other interconnections between 5-HT containing innervations with those of GABA and ACh may contribute to the development of movement disturbances (Fibiger and Lloyd, 1984; Schreiber and Pick, 1995). However, these interconnections have yet to be clarified.

Just how SSRIs induce EPS and other movement disorders in some patients, but potentially improve parkinsonism and dystonia in others, remains unclear. Furthermore, were the mechanisms underlying SSRI-induced movement disorders as simple as illustrated here, the expectation would be that SSRI-induced movement disorders would be common. In fact, the rates of such movement disturbances remain quite low."

 

[Transposony]

why does one get akathisia with anti depressants like Sertraline?

Nobody knows. So, they are not going to ask about it on the USMLE.

 

[Phloston]

Well I'd discard your Lange Psychiatry if I were you. Propranolol is definitely wrong. The answer is D: lorazepam.

Quoting UpToDate:

"Akathisia — Akathisia is the most common form of EPS. It usually presents as motor restlessness with a compelling urge to move and an inability to sit still. Individuals with milder akathisia may describe a subjective feeling of restlessness but not show restless motor behavior. If patients do not demonstrate restless behaviors, the examiner should inquire if they pace frequently or if they have difficulty sitting still.

Treatment options for akathisia include:

• A cautious antipsychotic dose reduction, if feasible, should be attempted first, with close monitoring of the patient for exacerbation of psychotic symptoms.
• If decreasing the antipsychotic drug dose is unfeasible or inadequate, we suggest treatment with a benzodiazepine. Two small randomized trials of 26 patients with schizophrenia found benzodiazepine treatment to reduce symptoms of akathisia compared to placebo (NNT=1.2). Lorazepam can be started at 0.5 mg orally twice daily. If the symptoms do not resolve and the patient has not experienced side effects such as ataxia and sedation, the medication can be incrementally raised up to 6 to 10 mg/day. Since benzodiazepines such as lorazepam are associated with sedation, withdrawal seizures, a potential for addiction, and tolerance, patients should receive the lowest dose that reduces akathisia.
• In our clinical experience, a beta blocker such as propranolol or an anticholinergic drug such as benztropine can be used to effectively treat akathisia if a benzodiazepine is not effective."

---------------

The problem with many USMLE resources is that they're not up to date. On the actual wards, UpToDate is by far the Gold Standard, meaning clinical decisions made based off of it would never be held against you (unless there was obviously some blatant, patient-specific factor that needed to be taken into consideration that was overlooked).

 

[pathologyDO]

Well I'd discard your Lange Psychiatry if I were you. Propranolol is definitely wrong. The answer is D: lorazepam.

Quoting UpToDate:

"Akathisia — Akathisia is the most common form of EPS. It usually presents as motor restlessness with a compelling urge to move and an inability to sit still. Individuals with milder akathisia may describe a subjective feeling of restlessness but not show restless motor behavior. If patients do not demonstrate restless behaviors, the examiner should inquire if they pace frequently or if they have difficulty sitting still.

Treatment options for akathisia include:

• A cautious antipsychotic dose reduction, if feasible, should be attempted first, with close monitoring of the patient for exacerbation of psychotic symptoms.
• If decreasing the antipsychotic drug dose is unfeasible or inadequate, we suggest treatment with a benzodiazepine. Two small randomized trials of 26 patients with schizophrenia found benzodiazepine treatment to reduce symptoms of akathisia compared to placebo (NNT=1.2). Lorazepam can be started at 0.5 mg orally twice daily. If the symptoms do not resolve and the patient has not experienced side effects such as ataxia and sedation, the medication can be incrementally raised up to 6 to 10 mg/day. Since benzodiazepines such as lorazepam are associated with sedation, withdrawal seizures, a potential for addiction, and tolerance, patients should receive the lowest dose that reduces akathisia.
• In our clinical experience, a beta blocker such as propranolol or an anticholinergic drug such as benztropine can be used to effectively treat akathisia if a benzodiazepine is not effective."

---------------

The problem with many USMLE resources is that they're not up to date. On the actual wards, UpToDate is by far the Gold Standard, meaning clinical decisions made based off of it would never be held against you (unless there was obviously some blatant, patient-specific factor that needed to be taken into consideration that was overlooked).

So to clarify, are you saying that for the wards we need to realize lorazepam is the first line drug choice for akathisia whereas on the USMLE the correct answer would be propranolol?

 

[Transposony]

Well I'd discard your Lange Psychiatry if I were you. Propranolol is definitely wrong. The answer is D: lorazepam.

The fact that question itself was from Lange Psychiatry, I think that it is a "poorly made" question since USMLE will never give two choices both of which may be correct depending on which resource you are using (CMDT, Goodman Gilmans and Harrison-mention both Propranolol and Bezos).
So, IMHO both Propranolol and lorazepam are correct choices.
Also, I don't think USMLE will only put questions choices based on one resource like UTD but majority of reputable resources.
So, above question is highly unlikely to appear on Step 1.

On a separate note, I wonder why FA is silent on this?

 

[Apoplexy__]

So to clarify, are you saying that for the wards we need to realize lorazepam is the first line drug choice for akathisia whereas on the USMLE the correct answer would be propranolol?

Well I'd discard your Lange Psychiatry if I were you. Propranolol is definitely wrong. The answer is D: lorazepam.

On the wards, my attending only ever used propanolol for akathisia. I wouldn't say it's "definitely wrong" -- looks like they're both right.

 

[pathologyDO]

On the wards, my attending only ever used propanolol for akathisia. I wouldn't say it's "definitely wrong" -- looks like they're both right.

OK so either one could be right, they wont ask a dastardly question with both answer choices unless they're pure evil. Got it thanks.

 

[Mr. Mojo Risin]

OK so either one could be right, they wont ask a dastardly question with both answer choices unless they're pure evil. Got it thanks.

Agreed that it is unlikely that a question like this would come up. There simply isn't enough information to support choosing one over the other. Still, I suppose they could give a vignette of someone with lung disease or another condition in which propranolol is contraindicated, thereby making lorazepam a better choice.

 

[Phloston]

If I were ever asked that question on the wards, I would say "Lorazepam, propranolol and benztropine have all shown efficacy, however UpToDate currently cites lorazepam, initially in small doses, as Tx ahead of propranolol or benztropine. If lorazepam isn't effective, then propranolol or benzotropine can be used."

And if your consultant disagrees, then he or she disagrees, and we'd just keep our mouths shut because we're still just med students.