Thoughts on the Harvard Psychopharm algorithm?

[reca]

I was wondering what people's thoughts are on the Harvard psychopharm algorithm? Psychopharm Algorithms. I was looking at it for bipolar depression today and it's a little bit different than what a lot of my attendings recommend. It has lithium as the first line for bipolar depression but my understanding is that the data for lithium is strongest for acute mania and augmentation of depression and that there are better first line options for bipolar depression (olz/fluoxetine per Maudsley is the best, also quetiapine and lurasidone are first lines where I'm at). I couldn't find anywhere else recommending lithium as a first line for bipolar depression.

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[MLT2MT2DO]

I've never seen this Harvard Algorithm though googling it I find it interesting. Reading it they also mention that it is made by utilizing and constantly reviewing peer reviewed journals yet nothing is cited. From my limited practice and what I've read Lithium isn't great for depressive symptoms of Bipolar alone and generally I wouldn't use it unless SI is prominent. I do like it for prevention of depressive episodes in BPAD if appropriate, though. If acute depression was the main complaint I'd also be more likely to pick the likes of Seroquel or Lurasidone.

Just a heads up that Maudsley seems to just hedge their bets on this one and parrots the NICE guidelines for Symbyax, since there are multiple options in the lit (though lithium not being one of them) for first line medications.

Edit: To further add to this that Alogorithm: they also recommend Lithium in a manic state (sure great it's first line) but recommend skipping over it entirely for an SGA in a "mixed" state. I'd love if anyone smarter than me could shed some light on the thought process behind this. @splik

 

[Merely]

Wow I never knew such algorithms existed! Are these helpful? Should residents be commiting these to memory?

 

[MLT2MT2DO]

Wow I never knew such algorithms existed! Are these helpful? Should residents be commiting these to memory?

Stick with something like Stahl's or Maudsley's. I prefer the latter for actual clinical use as opposed to "text book studying".

 

[reca]

Wow I never knew such algorithms existed! Are these helpful? Should residents be commiting these to memory?

I just found out about it recently. If it's truly evidence based it seems like it would be helpful but I'm not sure about it after looking at the bipolar depression algorithm. Like I said, I haven't found much evidence to support lithium as a first line (let alone the first line) for bipolar depression so now I'm wondering about it overall. I was hoping someone with more knowledge than me would have more insight (into either the algorithm in general or using lithium first line for bipolar depression in specific).

 

[romanticscience]

I've used the algorithms. They are each based on individual published papers:

1. Ansari, A., Osser, D. N.: The psychopharmacology algorithm project at the Harvard South Shore Program: an update on bipolar depression. Harv Rev Psychiatry 2010; 18:36-55 Abstract

Here they discuss their reasoning. I believe lithium is recommended because of its long-term prophylactic benefit, as a balance between long-term course and acute-phase management.

Lithium has its strongest evidence for pure (ie, euphoric mania) and typical bipolar courses (ie, recurrent pure manias and depressions). Mixed states fair better with valproate, carbamazepine, and atypical antipsychotics. I've attached a good chapter on the mixed-states concept, which I find to be a bit of a contentious issue but has helped me clinically.

 

[hebel]

Are you guys clicking the boxes for each step? If you do, you'll find multiple cited references and their rationale for each step.

 

[MLT2MT2DO]

I've used the algorithms. They are each based on individual published papers:

1. Ansari, A., Osser, D. N.: The psychopharmacology algorithm project at the Harvard South Shore Program: an update on bipolar depression. Harv Rev Psychiatry 2010; 18:36-55 Abstract

Here they discuss their reasoning. I believe lithium is recommended because of its long-term prophylactic benefit, as a balance between long-term course and acute-phase management.

Lithium has its strongest evidence for pure (ie, euphoric mania) and typical bipolar courses (ie, recurrent pure manias and depressions). Mixed states fair better with valproate, carbamazepine, and atypical antipsychotics. I've attached a good chapter on the mixed-states concept, which I find to be a bit of a contentious issue but has helped me clinically.

My confusion comes in, in that for Bipolar depression they also recommend Lithium. I personally would not use monotherapy Lithium in any acute Bipolar state unless pure Mania. My confusion came where they rationalized using Lithium in an acute Depressive episode but not as much in a Mixed Episode....thus making Mixed Mania a complete outlier.

I get the reasoning of prophylactic benefit, but this doesn't really change the fact the the algorithm is recommending it in a current episode. Thank you for this paper

Are you guys clicking the boxes for each step? If you do, you'll find multiple cited references and their rationale for each step.

I didn't realize you could do this, I'll look into the references after I get home, though I do still believe the majority of papers do not support Lithium for monotherapy use in an acute bipolar depressive state.

Edit: Their reference for the reason they use Lithium for Bipolar depression is themselves (I missed romantic linking it)

1. Ansari, A., Osser, D. N.: The psychopharmacology algorithm project at the Harvard South Shore Program: an update on bipolar depression. Harv Rev Psychiatry 2010; 18:36-55 Abstract

 

[tellme_areyoufree]

My confusion comes in, in that for Bipolar depression they also recommend Lithium. I personally would not use monotherapy Lithium in any acute Bipolar state unless pure Mania. My confusion came where they rationalized using Lithium in an acute Depressive episode but not as much in a Mixed Episode....thus making Mixed Mania a complete outlier.

I get the reasoning of prophylactic benefit, but this doesn't really change the fact the the algorithm is recommending it in a current episode. Thank you for this paper




I didn't realize you could do this, I'll look into the references after I get home, though I do still believe the majority of papers do not support Lithium for monotherapy use in an acute bipolar depressive state.

Edit: Their reference for the reason they use Lithium for Bipolar depression is themselves (I missed romantic linking it)

1. Ansari, A., Osser, D. N.: The psychopharmacology algorithm project at the Harvard South Shore Program: an update on bipolar depression. Harv Rev Psychiatry 2010; 18:36-55 Abstract

Their reference is the paper where they argue for why that's the best supported course.

 

[TexasPhysician]

These algorithms are a very basic guide at best. Don’t spend more than 10 seconds on each in my opinion. Psych isn’t a basic algorithm field.

 

[birchswing]

Interesting they are forward enough to recongize NAC for OCD but don't mention inositol. I haven't used it myself, but there's good evidence for it. I know of some people in forums who have felt a virtual cure from 5-HTP and inositol, sometimes NAC as well. But inositol seems to be the heavy hitter.

 

[Jules A]

Interesting they are forward enough to recongize NAC for OCD but don't mention inositol. I haven't used it myself, but there's good evidence for it. I know of some people in forums who have felt a virtual cure from 5-HTP and inositol, sometimes NAC as well. But inositol seems to be the heavy hitter.

I haven't seen overwhelming data to indicate inositol has been efficacious which is unfortunate. It is a difficult disorder to treat, my patient education often includes anticipating a mild to moderate reduction in symptoms/improvement in function and accepting it is likely to wax and wane. Once again I believe it is crucial these patients, if their cognitive function supports, work with a strong therapist.

 

[Merovinge]

I was wondering what people's thoughts are on the Harvard psychopharm algorithm? Psychopharm Algorithms. I was looking at it for bipolar depression today and it's a little bit different than what a lot of my attendings recommend. It has lithium as the first line for bipolar depression but my understanding is that the data for lithium is strongest for acute mania and augmentation of depression and that there are better first line options for bipolar depression (olz/fluoxetine per Maudsley is the best, also quetiapine and lurasidone are first lines where I'm at). I couldn't find anywhere else recommending lithium as a first line for bipolar depression.

I'd say to answer your original question the data is better for Seroquel or Latuda than Lithium for bipolar depression and its great your attendings are teaching that. There still is the decreased suicide rate with Lithium, which is appealing, but doesn't make up for the significant difference in effect size on depression in my mind particularly since I'm not sure we'd even know of a decreased rate with the appropriate atypicals given how new the data is on them.

 

[deleted736562]

I don't think Lithium as a first line is a bad idea. If they respond, then you've got a medication with much better maintenance data and an added bonus with suicide prevention. It will also work well to prevent cycling into mania/hypomania. If they don't respond as well, you can think of adding an atypical on top.

 

[FlowRate]

Lithium may be first line but it's not adequate if things are acute (psychotic depression, mania, mixed mania).

 

[whopper]

Wow I never knew such algorithms existed! Are these helpful? Should residents be commiting these to memory?

No.
Unless you're green and you need some starting point. (I'm not criticizing anyone who's in this category, that's why you come to this website).

The problem I've seen with such algorithms is they're usually based on data that's years old. For example since it's come out more meds now have indications to treat Bipolar Disorder with Depression. Also despite the data with Latuda and Bipolar Depression I haven't had too much success with it and this is out of about 30 patients I've tried on it. Out of literally the 10th patient in a row where it didn't work I was thinking WTF.

It also turns out that many of the newer antipsychotics are currently being studied such as Rexulti and Fanapt for Bipolar Disorder with Depression.

In general I try to avoid Quetiapine because of the side effects almost no patients want, that is weight-gain and feeling like a zombie. Latuda's very expensive. I've had better success with other meds.

 

[reca]

No.
Unless you're green and you need some starting point. (I'm not criticizing anyone who's in this category, that's why you come to this website).

The problem I've seen with such algorithms is they're usually based on data that's years old. For example since it's come out more meds now have indications to treat Bipolar Disorder with Depression. Also despite the data with Latuda and Bipolar Depression I haven't had too much success with it and this is out of about 30 patients I've tried on it. Out of literally the 10th patient in a row where it didn't work I was thinking WTF.

It also turns out that many of the newer antipsychotics are currently being studied such as Rexulti and Fanapt for Bipolar Disorder with Depression.

In general I try to avoid Quetiapine because of the side effects almost no patients want, that is weight-gain and feeling like a zombie. Latuda's very expensive. I've had better success with other meds.

Thanks for the input. What is your first line for bipolar depression then? Lamotrigine? Everything else has notable weight gain, right?

 

[whopper]

Lamotrigine is on the table but the problem there is it takes weeks to get to the right dosage, and the patient needs to be compliant on the meds.

Vraylar recently got an indication for Bipolar Depression. My own success rate vs Latuda has been far higher with Vraylar. Problem are these meds are very expensive and several insurance companies require failure with at least one antipsychotic before they are tried.

Quetiapine works but expect huge amounts of weight gain, sedation and the pt c/o feeling zombified.

Lithium can work very well but I tend to reserve this for patients who have moderate to severe Bipolar Disorder due to the side effects and need for labs.

 

[Jules A]

With Latuda I'm mindful of 20mg possibly being activating but overall have seen a decent and quick response for bipolar depression especially nice considering the favorable metabolic side effect profile.

 

[clausewitz2]

With Latuda I'm mindful of 20mg possibly being activating but overall have seen a decent and quick response for bipolar depression especially nice considering the favorable metabolic side effect profile.

Also like all serotonergic neuroleptics in bipolar disorder it is easy to overshoot into too large of a dose that is actively unhelpful. I would not push it above 60 barring extraordinary circumstances, 40 seems to be the sweet spot for a lot of people.

 

[whopper]

A problem here is I've yet to see a pharmacological/physiological theory of Bipolar Depression other than that it's different from unipolar depression. (Despite this and despite what STEP-BD says, I've seen several people with Bipolar Depression get better with an antidepressant, and these people were solidly diagnosed. I've seen them manic myself, then later depressed and there was no drug abuse). The meds that are approved for Bipolar Depression don't have theories proposing why they work for that disorder. Yes they can say they bind a receptor but then shy away from saying that's why it treated Bipolar Depression. So hard to give a discerning opinion as to what med to give outside of what we see in studies and clinical experience.

Forgot to add this. Lamotrigine and lower-IQ patients don't mix well. No it's not physiology. That demographic usually is not compliant, doesn't get it through their head the risks of SJS even when warned, and if they get a rash they forget half the time the risks of SJS or they freak out over anything with their skin and call you incessantly over something that's likely nothing.

but overall have seen a decent and quick response for bipolar depression especially nice considering the favorable metabolic side effect profile.

Which is the exact reason why one person's limited perspective (in this case mine) should not cloud our opinions on meds. When I mentioned I had the 10th patient in a row where it didn't work that could've simply just been incredibly bad luck. Such things happen with small sample sizes.

 

[Liquid8]

I think algorithms are a useful reference when standard approaches do not work, but should also not be used as a by-the-numbers approach in preference over a patient’s individual circumstances. I would not normally initiate Lithium as a first line agent in Bipolar Depression, but I did have recent case where I did so.

Six months this particular patient ago ended up being an involuntary patient in the context of a first episode drug induced psychosis. At the time he was diagnosed with a Delusional Disorder and discharged on an antipsychotic depot, but became depressed with anhedonia and didn’t respond to antidepressants. Apparently he was so psychotic at the time of the admission that he wasn’t able to give any kind of coherent history, although as his partner was quite informative about the nature of his mood swings I did have to wonder if they actually engaged with her or not.

When I saw him for the first time about a month ago, he gave an extended history of grandiosity and other manic symptoms. Since discharge he’d stopped using drugs and there was no more psychosis, although the racing thoughts which had been the catalyst for drug use were ongoing although with a depressive and negative theme. Enquired more into the manic episodes, these were not all associated with drug use, and also peaks coincided with behaviour leading to job losses, but as there was no overarching connection between different employers the Delusional Disorder diagnosis appeared less likely. My previous dealings with patients with Delusional Disorder is that there has to be systematised delusions, and it doesn’t typically respond well to antipsychotics so the presentation didn't quite "fit" with what I had expected.

Bipolar disorder seemed to be the most likely diagnosis, and even though this patient had presented with a bipolar depression, the numerous past instances of mania had been the most problematic. A post psychotic depression also seemed plausible, but I was also concerned about the risks of a rebound mania if I decided to increase their antidepressant. I had thought about switching antidepressants, but wanted the patient to have some mood stabiliser cover first and he'd never been tried on one. I had also considered that the depot might have been responsible for the patient’s restricted affect and diminished emotional range, but was unable to remove that from the equation immediately.

I ended up starting the patient on lithium for exactly the reasons outlined in the guide and the results have been quite positive in the form of a gradual mood improvement and normalisation of the racing thoughts. The depot has since been ceased, and the antidepressant reduced without any issue.

 

[Merovinge]

I've had amazing luck with Latuda in the adolescent population. It's starting to be covered decently by some insurances or with co-pay cards and generic with wider coverage is on the horizon. Seroquel also works very well when sleep issues abound and folks are thin. It's not a huge niche but if your bmi is 18, you have BPD and you aren't sleeping, I tend to see marked results with Seroquel.

 

[whopper]

Not Bipolar Disorder, but corresponding the above with Seroquel...
I had a patient with poor sleep, depression, was underweight and had chronic GI sx of unknown etiology described as chronic irritation and had been through several doctors for over 10 years some being GI specialists who couldn't nail the problem. His sleep problems had been present his entire life and no prior doctor could get it better.

Mirtazapine, the med most patients don't want to try because of the weight gain and oversedation, well I tried it on him. He came 1 month later saying the med was a "game changer." He went from underweight to normal weight and not overweight, no depression, no GI problems anymore. So then a year later he told me he's gotten a few job promotions cause the overall improvements allowed him to increased his work productivity tremendously with his physical problems being much worse in this are before treatment vs his psychiatric problems, and his family even his kids say he's a completely different and better person. During that year he went from looking like a sick chemo-patient to a handsome metrosexual guy.

Every single side effect the guy got from the med was one he wanted. He wasn't overweight, he wasn't oversedated. I still don't know WTF was causing those GI sx or why he couldn't sleep before-hand.

One of the few rare times where a med and all of it's bad side effects hit the bulls-eye in what the patient needed.

 

[clausewitz2]

Not Bipolar Disorder, but corresponding the above with Seroquel...
I had a patient with poor sleep, depression, was underweight and had chronic GI sx of unknown etiology described as chronic irritation and had been through several doctors for over 10 years some being GI specialists who couldn't nail the problem. His sleep problems had been present his entire life and no prior doctor could get it better.

Mirtazapine, the med most patients don't want to try because of the weight gain and oversedation, well I tried it on him. He came 1 month later saying the med was a "game changer." He went from underweight to normal weight and not overweight, no depression, no GI problems anymore. So then a year later he told me he's gotten a few job promotions cause the overall improvements allowed him to increased his work productivity tremendously with his physical problems being much worse in this are before treatment vs his psychiatric problems, and his family even his kids say he's a completely different and better person. During that year he went from looking like a sick chemo-patient to a handsome metrosexual guy.

Every single side effect the guy got from the med was one he wanted. He wasn't overweight, he wasn't oversedated. I still don't know WTF was causing those GI sx or why he couldn't sleep before-hand.

One of the few rare times where a med and all of it's bad side effects hit the bulls-eye in what the patient needed.

Karl Leonhard describes an entity he called "hypochondriacal depression", by which he meant literally "below-the-chest depression". Presentation dominated to a surprising extent by abdominal complaints in people who did not appear ill and without clear pathology. This is a thing.

We had someone like this at our center recently whose mysterious abdominal pain ended up responding to ECT and who then kept relapsing until she got on maintenance ECT.

Something something enteric nervous system something something.

 

[downwithDTB]

Not Bipolar Disorder, but corresponding the above with Seroquel...
I had a patient with poor sleep, depression, was underweight and had chronic GI sx of unknown etiology described as chronic irritation and had been through several doctors for over 10 years some being GI specialists who couldn't nail the problem. His sleep problems had been present his entire life and no prior doctor could get it better.

Mirtazapine, the med most patients don't want to try because of the weight gain and oversedation, well I tried it on him. He came 1 month later saying the med was a "game changer." He went from underweight to normal weight and not overweight, no depression, no GI problems anymore. So then a year later he told me he's gotten a few job promotions cause the overall improvements allowed him to increased his work productivity tremendously with his physical problems being much worse in this are before treatment vs his psychiatric problems, and his family even his kids say he's a completely different and better person. During that year he went from looking like a sick chemo-patient to a handsome metrosexual guy.

Every single side effect the guy got from the med was one he wanted. He wasn't overweight, he wasn't oversedated. I still don't know WTF was causing those GI sx or why he couldn't sleep before-hand.

One of the few rare times where a med and all of it's bad side effects hit the bulls-eye in what the patient needed.

Malnutrition alone causes insomnia, low mood, cognitive impairment and a plethora of vauge GI sx. What was egg and what was chicken is this case is unclear.