Any mood or anxiety disorder sufferer I’ve ever known has had a keen interest in meds. Makes sense. Though certainly not intended to be a stand-alone remedy, they can have the quickest impact. Last week we began a discussion of the bipolar meds scoop from 2019. Let’s continue, and wrap it up…
Aspirin? Fewer studies, but fewer risks (stroke and bleeding primary). But, hey, how ’bout this? Aspirin improves sexual dysfunction in men using lithium.
We got our series rolling last week featuring the work of psychiatrist Chris Aiken, MD from Psychiatric Times. We’re going to finish by turning to Dr. Aiken’s follow-up article Novel Approaches to Bipolar: What Worked, and What Did Not, in 2019.
Dr. Aiken is the director of the Mood Treatment Center and an instructor in clinical psychiatry at the Wake Forest University School of Medicine. You need to know that Dr. Aiken doesn’t accept honoraria from pharmaceutical companies.
Let’s get busy…
Novel Approaches to Bipolar: What Worked, and What Did Not, in 2019
Dr. Aiken kicks things off by emphasizing that his first article, which we reviewed last week, addressed traditional interventions. The target of this go-round is novel approaches in the treatment of bipolar disorder. Remember, this is within the context of 2019.
N-acetylcysteine: Down, but Not Out
The anti-inflammatory N-acetylcysteine (NAC) is the primary antioxidant in the brain. It’s used to treat acetaminophen overdose, as well as respiratory and lung conditions. NAC has been studied as a treatment for numerous psychiatric disorders, including bipolar.
Well, according to Dr. Aiken NAC was the biggest floparoo of 2019. Seems it failed in three controlled trials of bipolar depression. And that’s a disappointment, given it showed promise in a 2008 trial.
Specifically, NAC ended-up working at month six for patients with subsyndromal depression who weren’t in full depressive episodes. Aiken cites this gem from the 2008 study: those who got better felt worse within four weeks of stopping NAC. Hmmm.
Anti-inflammatories and Mitochondrial Therapies: Mixed Results
Dr. Aiken states NAC is a component of two developing stories in bipolar disorder: inflammation and mitochondrial dysfunction. Both play a role in the generation of bipolar and both are positively impacted by NAC.
But there were other anti-inflammatories put to the test in 2019. Celecoxib (Celebrex) and aspirin showed positive results as augmenting agents in bipolar depression. This underscored results from prior research.
Celecoxib was dosed at a twice daily 200 mg in augmenting escitalopram (Lexapro). Aspirin was dosed at a once daily 1000 mg as a NAC add-on. 81 mg twice daily worked in an earlier trial in the augmentation of minocycline (Minocin).
So much for the good news. The anti-diabetic agent pioglitazone (Actos) may have fared well in a 2015 trial, but crashed in 2019. Atorvastatin (Lipitor), despite having some nice earlier trial results for depression and cognition, failed to repeat in 2019. The 2019 trial focused upon cognitive function in bipolar and unipolar depression. Incidentally, it’s atorvastatin’s anti-inflammatory properties that deliver the psychiatric effects.
Okay, the mitochondrial theory. Eh, it didn’t produce in 2019. In the NAC trials, a cocktail of sixteen nutraceuticals with potential mitochondrial benefits was tested. Though included were compounds with known anti-depressant effects, the cocktail didn’t separate from placebo.
The Take-Away
According to Dr. Aiken, the role of NAC in bipolar disorder treatment has been clipped, but not tossed-out. Fact is, NAC is one of a handful of therapies that can work for subsyndromal depressive symptoms – common particularly in bipolar II.
In animal studies, NAC also protected the kidneys against lithium toxicity. By the way, NAC is safe, low-cost, and well-tolerated.
Aiken reports that celecoxib is one of the better-studied anti-inflammatories for the treatment of bipolar and unipolar depression. Keep in mind, it’s better suited for short-term use, as using it long-term can increase the risk of stroke, heart attack, internal bleeding, and possible kidney toxicity. Still, short-term use needs to be reserved for treatment-resistant cases.
Aspirin? Fewer studies, but fewer risks (stroke and bleeding primary). But, hey, how ’bout this? Aspirin improves sexual dysfunction in men using lithium.
As he did in his first piece, Dr. Aiken has produced and provided a helpful chart…
Let’s Take It Home
I understand how much the development of meds for the mood and anxiety disorders means to anyone reading this. Don’t forget, I’ve been on this merry-go-round for a long time.
Yes, I know there weren’t any revelations in the series that would have you crack open the champagne. But given our current knowledge of the brain, and the rest of the body, we have to accept in-by-inch progress. I mean, what choice do we have? And you know what? I’m pleased creative research continues.
In the meantime, look to meds, but don’t forget they aren’t the only game in town. Be sure to research and implement non-med options as indicated.
Oh, before we part company: Do you think your psych med prescriber stays current on research? If you don’t, why not talk about it? Heck, bring articles like this to appointments. Just sayin’…
I f you’re being tormented by a mood or anxiety disorder, you’re likely interested in the happenings on the meds front. Who could blame you?! Often, unipolar depression and anxiety get top billing. But we’re going to take a look at the scoop from 2019 for bipolar disorder meds. Let’s roll…
Compared with other mood stabilizers, those using lithium had 50% fewer suicide attempts, better functioning, and less depression and aggression.
We have lots of information to review, so we need to get right into it. But I have to mention that reference for this piece is an article from Psychiatric Times, Bipolar Disorder: Practice-Changing Trials from 2019.
The piece was written by Chris Aiken, MD. Dr. Aiken is the director of the Mood Treatment Center and an instructor in clinical psychiatry at the Wake Forest University School of Medicine. It’s important to know that Dr. Aiken doesn’t accept honoraria from pharmaceutical companies.
Now, Dr. Aiken has written another article pertaining to the bipolar disorder meds scoop from 2019. I was going to review it here, but it would have made for a very long piece. So stay tuned, I’ll be back with “Part 2” in a handful of days.
Bipolar Disorder: Practice-Changing Trials from 2019
As in the original article, we’re going to do quick highlight summaries. Of note, Dr. Aiken points-out that in addition to official FDA decrees, over a dozen randomized controlled trials on bipolar disorder meds were released in 2019.
Cariprazine in Bipolar I Depression
Cariprazine (Vraylar) has been studied for bipolar depression since 2009. Results have been largely positive for the 1.5 mg daily dose. Interestingly enough, raising the dose to 3 mg daily doesn’t increase efficacy. There was a new trial in 2019 that produced essentially the same findings.
It seems compared to other atypical antipsychotics, cariprazine’s advantage is its tolerability, as well as proven efficacy in relieving both depression and mania.
Atypical Antipsychotic Augmentation Post-Mania
According to an analysis of a 2016 study, when risperidone (Risperdal) was used to augment a mood stabilizer in the treatment of mania it prevented relapses for up to six months. Longer use (up to a year) only resulted in additional weight gain.
Dr. Aiken says this provides a different spin on the maintenance story, because earlier studies stopped the antipsychotic after two to three months. So it wasn’t clear if the med could be safely stopped at a later point. Now we know that discontinuation at six months is feasible – with a slow taper. Dr. Aiken recommends lowering the dose every two weeks, keeping the original mood stabilizer in place.
Lithium & Children
In a trial of children aged seven to twelve, lithium, in contrast to risperidone, kept working to prevent manic episodes after six months.
Separately, lithium performed well in a large study from 2019 that followed youth with bipolar disorder for an average of ten years. Compared with other mood stabilizers, those using lithium had 50% fewer suicide attempts, better functioning, and less depression and aggression.
Carbamazepine/Lithium: Reborn
Carbamazepine (Tegretol) and valproate (Depakote) have been used to augment lithium for years. Thing is, the two were never compared head-to-head until 2019.
The number of study subjects was small, but validity was supplied by a long duration. Pertaining to mania and depression, both anticonvulsants performed similarly. However, carbamazepine was better tolerated in terms of weight gain, fatigue, and sexual dysfunction.
Thyroid Augmentation for Anxiety
Supraphysiologic (greater than normally present in the body) thyroid doesn’t sound like a good idea for someone struggling with anxiety. However, a 2019 study – analyzing a 2014 trial – found it didn’t worsen anxiety, and anxiety symptoms didn’t predict antidepressant effects. So it appears as though levothyroxine (Synthroid) may be helpful for bipolar depression.
TMS Doesn’t Harm Cognition – Might Even Help
Bipolar depression responds to both electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS). But ECT is limited by its cognitive effects. Not only did a 2018 study show that TMS in bipolar disorder didn’t cause cognitive deficits, a 2019 study found that for euthymic bipolar patients, TMS actually improved cognitive measures.
Rivastigmine & Memantine
Dr. Aiken quickly mentions the anti-dementia drugs rivastigmine (Exelon) and memantine (Namenda) for the treatment of bipolar mania. He says the trial results were either not significant or not clinically significant. He’ll pass on both until more data is available.
Dr. Aiken created and included the following chart in his article. Great reference material…
So There You Have It
If you’re doing all you can to manage bipolar disorder, I’m thinking you found what we reviewed relevant and helpful. Knowledge always is, not to mention all-out powerful.
As I said, look for Part 2 of this series in several days. It includes even more valuable information from Dr. Aiken.
Diabetes, hypothyroidism, anemia: if the lab results say you have it, you have it. The emotional and mental disorders? Uh, no. For instance, the symptoms, and their overlap, of ADHD, bipolar disorder, and borderline personality disorder. I mean, which is it?
And for an accurate differential diagnosis (distinguishing a disorder from others that present with similar clinical features), Marangoni recommends the clinician rely upon – you guessed it – signs and symptoms, age of onset…
What would any of us give to have our bipolar disorder, depression, or generalized anxiety diagnosis based upon lab work or imaging? Of course, interventions remain dicey, but at least we’d have a lock on what’s ailing us.
Now, I believe scientists are working on it; however, diagnosing the emotional and mental disorders can be a signs and symptoms, age of onset, family history, etc. guessing game.
And that’s a dark veil over an already troubling set of circumstances.
In an effort to resolve some confusion in one particular neck of the diagnostic woods, I’m going to summarize a fairly recent article from Psychiatric Times. “ADHD, Bipolar Disorder, or Borderline Personality Disorder” was written by Italian psychiatrist Ciro Marangoni. I’ll slip you a link at the end.
“Significance For Practicing Psychiatrists”
Dr. Marangoni begins his piece with a can’t miss yellow box with the heading, SIGNIFICANCE FOR PRACTICING PSYCHIATRISTS. In it, Marangoni emphasizes the high prevalence of ADHD, bipolar disorder (BD), and borderline personality disorder (BPD) in juveniles and young adults.
He goes on to say that comorbidity (coexistence) between the three is frequent, which impairs treatment response and recovery. And for an accurate differential diagnosis (distinguishing a disorder from others that present with similar clinical features), Marangoni recommends the clinician rely upon – you guessed it – signs and symptoms, age of onset, family psychiatric history, etc. – as well as locomotor activity and sleep pattern.
Okay, let’s get our business handled by cherry-picking Dr. Marangoni’s discussion of ADHD, BD, and BPD…
Attention-Deficit/Hyperactivity Disorder
Generally speaking, a diagnosis of ADHD, which persists into adulthood in 50% of cases, is based upon life-interrupting levels of inattention, hyperactivity, and impulsivity. But diagnosing ADHD becomes much more difficult when you toss in lesser known symptoms such as irritability, emotional dysregulation, frequent mood changes, low frustration tolerance, poor self-esteem, and sleep problems.
And keep in mind, hyperactivity is characterized by phenomena such as restlessness, fidgeting, talkativeness, poor inhibition, and engaging in risky behaviors. So, the diagnostic process can become complicated.
Already, can you see the symptom overlaps with what you believe you’d find in BD and BPD?
Now, before we move on to them, here’s an extremely informative and helpful table Dr. Marangoni included in his article. It’s definitely a keeper…
Bipolar Disorder
Dr. Marangoni begins his discussion of BD by noting its episodic nature. He observes that some patients experience chronic, unremitting symptoms, while others may go weeks or months with reduced or no symptoms at all. Thing is, the diagnostic requirement of recurring episodes (manic, hypomanic, major depressive) often results in misdiagnosis of patients with a chronic, non-episodic presentation.
I’m thinking most of us know the symptoms of depression, but that may not be the case for mania and hypomania. In making his point, Marangoni includes euphoric and mixed (manic and depressive) mood states, talkativeness, decreased need for sleep, impulsivity, irritability, hyperactivity, and risky behaviors.
Are you still on board with symptom overlap? Now to BPD…
Borderline Personality Disorder
The good doctor begins his BPD chat by observing that the DSM-5 says a BPD diagnosis shouldn’t be made before age 18. According to him, it’s acceptable if symptoms are clear and persistent.
So what does BPD look like? How ’bout this from Marangoni? It’s a chronic and pervasive pattern of instability in interpersonal relationships, mood, and self-esteem – with significant impulsivity. And then there’s ramped-up risk for self-harm, suicide, feelings of abandonment, anger/rage, and come-and-go stress-induced psychotic symptoms.
Marangoni goes on to emphasize the features of BPD that overlap with ADHD. These include a chronic course, emotional instability, impulsivity, and risk-taking behaviors.
In fact, patients with BPD may experience their own special kind of inattention as part of dissociative states when they’re feeling emotionally stressed. This particularly presents in response to feelings of rejection, failure, and loneliness. By comparison, symptoms of inattention in ADHD are often seen in situations that lack external stimuli (e.g., during boring, routine, or familiar tasks).
When it comes to alleviating stress and tension, those with BPD typically turn to self-injurious behavior. ADHD patients are more likely to regulate their emotions via extreme sports, novelty seeking, sexual activity, and aggression.
Finally, though not in the DSM-5, a combination of BPD and BD is now being recognized – and referred to as borderpolar.
All Set
I long for the day when diagnosing emotional and mental health disorders becomes as routine and reliable as identifying diabetes, hypothyroidism, and anemia. Someday, right?
In the meantime, we have to do the best we can with what we have, and trust that our clinicians stay informed and maintain a sharp eye. And we can help them by sharing specific details about what we’re experiencing.
If you’re dealing with ADHD, bipolar disorder, or borderline personality disorder – or wondering if you are – I hope this information is helpful.
Be sure to take a look at Dr. Marangoni’s article. No way could I squeeze everything into this piece, including his discussion of treatment.
Who could even imagine that child having an emotional/mental disorder? Actually, he may. And it’s quite possible that disorder is “bipolar.” It’s a contentious call, so let’s address the controversy with reliable information. I think you’ll find the following thought-provoking…
It can’t be emphasized enough that early intervention is everything when it comes to the treatment of juvenile bipolar disorder. But the sad reality is diagnosis and treatment are most often delayed for many years.
“There’s no way a child can have bipolar disorder, or any mental illness. And anyone who gives him meds should be thrown in jail.”
Well, a lot of folk believe that. But a lot of folk love and care for children with bipolar disorder, and other emotional/mental situations – and give them meds.
How ’bout we slow things down and toss some reliable information at the issue?
The Juvenile Bipolar Research Foundation (JBRF) is the first and only non-profit foundation dedicated solely to promoting research to identify the source of early-onset bipolar disorder. Researching treatments is also a part of their scientific work.
By chance, I came across their website and knew I had to get it on Chipur. All of what you’re about to read is grounded in JBRF’s work.
Juvenile Bipolar Disorder: Diagnosis
Within the realm of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), bipolar disorder is classified as an adult mood disorder. However, it’s noted, “Special considerations are necessary to detect the disorder in children.”
The reason for the adult exclusivity? Well, until relatively recently it was believed children couldn’t experience symptoms of mania.
Fact is, some children actually do meet the “adult” criteria for both bipolar I and II. However, in the majority of cases, children present with symptom variations that don’t quite meet the DSM standard (e.g.: manic or depressed mood doesn’t last long enough, don’t exhibit manic grandiosity). So let’s just say the typical childhood version looks, well, different.
So if formal juvenile bipolar disorder criteria existed, it might include the following…
Abrupt swings of mood and energy that occur multiple times within a day
Switching from irritable, easily annoyed, angry mood states to silly, goofy, giddy elation; or fluctuating closer to one pole or the other
Low energy periods of intense boredom, sleep disturbance, difficulty in getting out of bed, depression, social withdrawal, low self-esteem, suicidal thoughts
Psychotic symptoms such as delusions and hallucinations
Keep in mind, all criteria don’t have to be met to quality for a diagnosis.
Juvenile Bipolar Disorder Treatment
It can’t be emphasized enough that early intervention is everything when it comes to the treatment of juvenile bipolar disorder. But the sad reality is diagnosis and treatment are most often delayed for many years.
During that delay, diagnoses are offered such as ADHD, OCD, major depressive disorder, separation anxiety disorder, oppositional defiant disorder, conduct disorder, and more. And the real tragedy is, indicated meds for those disorders are prescribed, and they often make the child’s bipolar disorder worse.
Okay, let’s say a diagnosis of juvenile bipolar disorder has been made. Now what?
Priority-one is stabilizing mood and treating sleep disturbance and psychotic symptoms, if they exist. When that’s handled, a therapy that helps the child understand their illness and how it impacts their emotions and behaviors is really important.
Mood stabilizers are crucial in the treatment of adult bipolar disorder. Since they’ve only recently begun to be used in children, there isn’t a whole lot of data regarding efficacy, side effects, etc. But, it’s interesting to note that anticonvulsant mood stabilizers such as Depakote and Tegretol have been used to treat young children with epilepsy. So at least there’s data available for the population.
These days, many psychiatrists adapt their knowledge of adult treatment of bipolar disorder to children, prescribing very cautiously. Commonly prescribed meds include lithium carbonate (Lithobid, Lithane, Eskalith), divalproex sodium (Depakote, Depakene), carbamazepine (Tegretol), oxcarbazapine (Trileptal), gabapentin (Neurontin), lamotrigine (Lamictal), topiramate (Topamax), and tiagabine (Gabitril).
Should the child be experiencing psychotic symptoms and/or aggressive behavior, atypical antipsychotics such as aripiprazole (Abilify) and quetiapine (Seroquel) may be used. Benzodiazepines such as clonazepam (Klonopin) and lorazepam (Ativan) may be prescribed for troubling anxiety states, sleep disturbance, and rapid-cycling swings in activity or energy.
Antidepressants? Risky business, due to the potential for mania, hypomania, rapid-cycling, irritability, aggression, and more. Some children may be able to handle an antidepressant for a short time if it’s accompanied by a mood stabilizer.
Please know I didn’t list those meds with an “Oh well” shrug of the shoulders. Psychotropic meds for children isn’t an easy subject to approach. However, if a child is in severe emotional/mental pain – even posing a threat to self or others – approach it we must.
Let’s Wrap It Up
Yes, any child could have an emotional/mental disorder, and it could be “bipolar.” As controversial an issue as it may be, it simply can’t be ignored.
What a break, coming upon the Juvenile Bipolar Research Foundation website. There’s a ton of information available. Please take the time to tap-in, especially if you’re concerned about a child close to you. And you may want to make a donation.
If you enter “bipolar” in the Chipur search box you’ll find plenty of titles, but not enough. Fact is, bipolar disorder doesn’t get its due, and I think we need to do something about it. Let’s begin to put up our dukes by reviewing some troubling, then hopeful, new research…
These superhighways that come from the insula that go mainly to the pre-frontal cortex – which is an area for decision making and personality – they’re weaker in people at high risk for bipolar disorder.
Bipolar disorder has got to be hard, just hard. I mean, it’s one thing trying to manage mood cycling and the struggles within each episode. But then there’s the meds factor, which often becomes a low odds of winning crap-shoot.
I’ll say it again, bipolar disorder doesn’t get its due – in the therapy and psychiatry office, in the literature, and in society in general.
Okay, in commencing Chipur efforts to “put up our dukes” and make a difference, let’s take a look at two important pieces of recent research…
A Six Year Delay Between Onset and Diagnosis? Yikes!
In a study published in the Canadian Journal of Psychiatry, researchers from the University of New South Wales (Australia) and St. John of God Research Centre (Italy) revealed some stunning findings. Led by Dr. Matthew Large and Dr. Giovanni de Girolamo, the research team discovered that people presenting with symptoms of bipolar disorder are waiting an average of six years before diagnosis and treatment.
Mind you, this is a meta-analysis that included 9,400 patients from 27 studies. Those are respectable numbers.
According to team leader Dr. Large, the treatment delay is often longer for young people. And that’s because parents and physicians often mistake “moodiness” for the ups-and-downs of being a teen.
From Dr. Large…
This is a lost opportunity because the severity and frequency of episodes can be reduced with medication and other interventions.
While some patients, particularly those who present with psychosis, probably do receive timely treatment, the diagnosis of the early phase of bipolar disorder can be difficult. This is because mental health clinicians are sometimes unable to distinguish the depressed phase of bipolar disorder from other types of depression.
The diagnosis of bipolar disorder can also be missed because it relies on a detailed life history and corroborative information from carers and family, information that takes time and care to gather.
What to do about the dilemma?
Well, the team challenges clinicians to look more closely at a patient’s history of mood symptoms, looking for distinct changes in mood, as well as other risk factors. These could be family history, mood swings caused by external events such as antidepressant treatment, overseas travel and recreational drug use. And a consistent approach to recording symptom onset is essential.
So that’s the scoop on diagnosis and treatment delay. Let’s move-on to some recent research addressing early detection of a high-risk of bipolar disorder…
The Seeds of Image-Based Diagnostic Testing
A hopeful study pertaining to early detection and treatment of bipolar disorder by researchers from QIMR Berghofer Medical Research Institute (Australia) and the University of New South Wales was recently presented in the journal Molecular Psychiatry.
The study reveals that those of highest risk of developing bipolar disorder exhibit weak connections in the emotional areas of the brain. It’s hoped that the findings will foster the development of new tools to identify and manage those risks before disorder onset, and aid in reducing impact once it presents.
And how ’bout this? The ultimate goal is to develop image-based diagnostic tests for bipolar disorder. Can you image?!
The study team used MRI scans on the brains of some 200 people who had a first-degree relative with bipolar and who were at high-risk themselves (along with a control group). Discovered were networks of weaker connections between brain regions involved in regulating emotional and cognitive processes. The team will annually follow-up with study participants to see if the brain changes will generate episodes of mania.
According to team lead Dr. Michael Breakspear…
At the moment we don’t have any markers or tests for predicting who is at risk of developing bipolar disorder, as we do for heart disease. If we can develop a tool to identify and confirm those who are at the very highest risk, then we can advise them on how to minimise their risk of developing bipolar, for example, by avoiding illicit drugs and minimising stress.
These discoveries may open the door to starting people on medication before the illness, to reduce the risk of manic episodes before the first one occurs. It’s crucial that we diagnose people correctly straight away so they can start receiving the right treatment.
Dr. Breakspear highlights one particular brain component and its connections – the insula. According to the doc, it’s the part of the brain where we feel our body physiology.
More from Dr. Breakspear…
These superhighways that come from the insula that go mainly to the pre-frontal cortex – which is an area for decision making and personality – they’re weaker in people at high risk for bipolar disorder.
A lot of the connections come back to the insula, and they’re sort of inhibitory connections. So they’ll sort of say, ‘You know you’re in a business meeting, so inhibit the emotional fluctuations that you have.’ And if those connections aren’t strong enough, then the thinking is that the emotions sort of burst through and people get elated and they get depressed and their behaviour is disinhibited.
This is just fascinating – and huge. And the best part is, Dr. Breakspear hopes imagery and blood tests can be used within five to 10 years to confirm those at highest risk of developing bipolar disorder. These folk could then be offered assistance such as lithium to prevent mania, along with non-med interventions.
We’ll Close Now
I’d say we put up our dukes, wouldn’t you? At least on Chipur we’ve commenced really giving bipolar disorder its due. And it more than deserves it.
Two stories, one responding to the other. Waiting six years before diagnosing and treating bipolar disorder is just wrong. But knowing work is being done toward confirming high-risk is heartening – and essential.
It’s time to bring bipolar disorder out of the shadows. What will you do to shine a light and carry-on the fight?
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Dr. Aiken states NAC is a component of two developing stories in bipolar disorder: inflammation and mitochondrial dysfunction. Both play a role in the generation of bipolar and both are positively impacted by NAC.
A hopeful study pertaining to early detection and treatment of bipolar disorder by researchers from QIMR Berghofer Medical Research Institute (Australia) and the University of New South Wales was recently presented in the journal Molecular Psychiatry.
