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[Music] I'd wager a guess that every single one of you listening has helped manage a patient with bipolar depression who also has significant anxiety. Anxiety and bipolar is so often a challenge given the mainstay medications are SSRI and don't usually play so well with bipolar. Today we're diving into this crucial area.
managing bipolar depression when anxiety is also a major player. Our focus today is on a recent post hawk analysis published in the journal of affective disorders titled larazzidone for bipolar 1 depression with comorbid anxiety symptoms post hawk analysis of randomized placeboc controlled studies. This paper offers some really valuable insights into using laorazzidone in these challenging cases. I'm Kristen Raj for the Psychopharmarmacology Institute and this is quick takes.
So why is this topic so important? Well, anxiety comorbidity is incredibly common in bipolar disorder with one study in this paper noting that about 37.5% of patients with bipolar 1 depression also have severe anxiety symptoms. And when anxiety is present, it's not just an added symptom. It's associated with a whole host of adverse outcomes, greater illness severity, reduced treatment response, increased functional impairment, and even a higher risk of suicide attempts. The DSM5 even includes anxious distress as a specifier for bipolar depression, highlighting its clinical significance.
Current guidelines like those from Canaten ISBD emphasize prioritizing mood stabilization before tackling specific anxiety symptoms. While we have some options like katiapene and alanthopene combination that have shown preliminary efficacy for anxiety and bipolar depression, evidence-based options remain limited. This is where this paper sheds new light.
The Razdown is already approved worldwide for schizophrenia and bipolar depression and previous studies hinted that it has anti-depressant and anxiety reducing powers. The big question was does it work for bipolar depression specifically when anxiety is a major player too? This was a post hawk analysis, meaning the researchers went back and looked at pulled data from two previously conducted six-week randomized double blind placeboc controlled studies on laorazzone monotherapy for bipolar one depression. They divide patients into two groups based on their baseline Hamilton anxiety rating scale or ham a score. a severe anxiety group with a hamme score of 18 or higher and a non severe group with a ham score below 18. Turns out about a third of patients had that severe anxiety at baseline.
The original two studies both tested two different dose ranges of laurazzone. a lower dose range of 20 to 60 milligs per day and a higher dose range of 80 to 120 mg per day against placebo over 6 weeks. The key questions they wanted to answer were how effective and safe is laorazzone in patients with bipolar depression regardless of their anxiety severity and specifically does the lower dose range of laorazzone 20 to 60 milligs per day show significant antepressant and anxolytic efficacy in those with severe anxiety.
So, first off, here's the exciting part about how it helped with depressive symptoms measured by the Modric score. For the severe anxiety crew, the lower dose of Laorazzone, 20 to 60 milligs, really shined. Patients on this dose saw a significant improvement in their depression scores, making a noticeable difference. They also had a significantly higher rate of response or at least 50% improvement with a number needed to treat of five and even reaching a state of remission where depression symptoms were very low to non-existent with a number needed to treat of seven compared to placebo.
Interestingly, the higher dose range 80 to 120 millig did not show the same significant benefit for severe anxiety group. for the non- severe anxiety group. Good news here too. Both the lower dose range and the higher dose range of laorazzone significantly improved depression scores. Both doses also led to much better response and remission rates compared to placebo. Number needed to treat for response was five for the lower dose and six for the higher. And the number needed to treat for remission was eight for the lower dose and seven for the higher.
And what about those pesky anxiety symptoms measured by the HAM A? For the severe anxiety group, again, the lower dose of laorazzone, 20 to 60 millig, was superior, significantly reducing anxiety scores. The higher dose didn't quite hit statistical significance for anxiety in this group. For the non- severe anxiety group, both doses of laorazzone showed a significant improvement in anxiety symptoms.
So the big takeaway for effectiveness, the sources really emphasize that laorazzone at 20 to 60 milligs per day appears to be effective for both depressive and anxiety symptoms and bipolar one depression, no matter if your anxiety is severe or not. It's pretty cool because this is especially helpful given how tough it can be to treat bipolar depression when anxiety is prominent. Plus, it seems to keep those symptoms at bay in the long run during the open label extension phases.
In terms of safety and tolerability, the study found larazzone to have a generally good safety profile. The most common adverse events were acthesia and nausea. Importantly, they found minimal changes in metabolic laboratory parameters or body weight. The range of treatment emergent mania was also low. When comparing larazzone to other common treatments like the lanspine fluxene combination or katiapene, this paper highlights that while the antid-depressant effect might be comparable, the razzone stands out regarding metabolic safety. Alanspinoxine and kyapene are associated with notably higher weight gain and risk of metabolic adverse events compared to larone.
Now why the difference with the higher dose in severe anxiety being less effective than the lower dosing? both for depression and anxiety. The source suggests a couple of possibilities. It could be a type 2 error, meaning the sample size for that specific subgroup was a bit small, so it was harder to detect a significant effect. Or perhaps the higher dose, 80 to 120 mg, might cause too much blockade of D2 receptors, which has been linked to dysphoria. This could also explain why athesia, that restless feeling, was more than twice as prevalent with a higher dose in the severe anxiety group. Athesia symptoms like nervousness and inner tension can overlap with anxiety symptoms, potentially diminishing overall efficacy at higher doses. This makes sense with other research suggesting that for bipolar depression, optimal effects might be seen at doses like 40 to 60 mg, even though higher doses are good for schizophrenia.
So, a clinical pearl takeaway for our patients with bipolar depression and significant anxiety. Starting at the lower end of the laurazzone dose range, 20 to 60 millig per day, appears to be more effective and better tolerated than higher doses. More isn't always better, especially when we're dealing with the nuanced neurobiology of anxiety.
Now, as with any research, it's important to look at the limitations. This was a post hawk analysis, which means the results need to be confirmed by dedicated prospective trials. Also, while the extension studies hinted at sustained effects, the long-term open label phase lacked a placebo control group. So, we can't draw definitive conclusions about long-term efficacy from that data alone. and the definition of severe anxiety was based on a HAM a score, not a formal DSM5 diagnosis. Finally, the study population was recruited using specific criteria. So, generalizability to all of your patients in the community might be somewhat limited.
[Music] So, what's our main takeaway for your practice? This post hawk analysis strongly suggests that laorazzdone in the 20 to 60 mgram per day range is an effective treatment option for patients with bipolar one depression even those with severe comorbid anxiety symptoms. It effectively addresses both depressive and anxiety symptoms and it does so with a generally good safety profile particularly regarding metabolic parameters for your patients struggling with anxiety alongside their bipolar depression. Remember that the lower dose range appears to be the sweet spot, potentially offering better efficacy and fewer side effects like athesia, especially in those with higher baseline anxiety. Thank you for joining me on QuickTakes. I hope this discussion provides you with a helpful tool for your clinical toolkit.