Bipolar

Bipolar (also known as Bipolar Affective Disorder or Manic Depression) is a diagnosis given to people with a cyclic mood disorder. Most commonly, a person experiences a very low mood – similar to major depressive disorder, with intermittently feeling somewhat okay, and sporadically the person will become manic.

Bipolar depression : persistent sadness, loss of interest or pleasure in activities and feelings of very low energy

Mania: over-the-top level of activity or energy, extreme happy mood and odd behavior, often risk taking; sometimes includes hearing voices, paranoia or psychosis

Hypomania: a mild form of mania, the person is more elated and or hyperactive than average people, but not to the level of mania

These moods are significantly different to your middle mood

What is in a Bipolar Diagnosis

While the diagnostic criteria for BPAD are fairly clear, the symptoms are similar enough to several other conditions that it is not uncommon for someone to be misdiagnosed. The most common conditions that are misdiagnosed as BPAD are ADHD (Attention Deficit Hyperactivity Disorder), PMDD (Pre-Menstrual Dysphoric Disorder) and MDD (Major Depressive Disorder).

The USA DSM 5 (Diagnostic and Statistical Manual of Mental Disorders ver 5) has two major variants Bipolar 1 (with at least 1 manic episode) and Bipolar 2 (without a manic episode). Each of these has several subtypes.

  • Bipolar 1
    • At least 1 manic episode
    • Patient may have hypomanic episodes are common in BPAD, as are major depressive episodes, but are not required
  • Bipolar 2
    • No manic episodes
    • At least 1 hypomanic episode and at least 1 major depressive episode

The person diagnosed must not already be diagnosed with any of the spectrum conditions of schizophrenia or psychosis.

First we need to understand what manic, hypomanic and depressive means in term of Bipolar. Click “>” below to expand each.

Manic / Mania

Witnessing a manic episode is truly an odd experience. The person is not just happy, they are super ecstatics, or super irritated etc. This is an extreme presentation that stands out from the expected average range of human behaviour and affect.

To be considered mania, the elevated, expansive, or irritable mood must last for at least one week and be present most of the day, nearly every day.

From the DSM 5 definition of Mania re Bipolar

A. A distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently goal-directed behavior or energy, lasting at least 1 week and present most of the day, nearly every day (or any duration if hospitalization is necessary).

B. During the period of mood disturbance and increased energy or activity, three (or more) of the following symptoms have persisted (four if the mood is only irritable) are present to a significant degree and represent a noticeable change from usual behavior:
1. Inflated self-esteem or grandiosity
2. Decreased need for sleep (e.g., feels rested after only 3 hours of sleep)
3. More talkative than usual or pressure to keep talking
4. Flight of ideas or subjective experience that thoughts are racing
5. Distractibility (i.e., attention too easily drawn to unimportant or irrelevant external stimuli), as reported or observed.
6. Increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation
7. Excessive involvement in activities that have a high potential for painful consequences (e.g., engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments)

C. The mood disturbance is sufficiently severe to cause marked impairment in social or occupational functioning or to necessitate hospitalization to prevent harm to self or others, or there are psychotic features.

D. The episode is not attributable to the direct physiological effects of a substance (e.g., a drug of abuse, a medication, or other treatment) or another medical condition.
Note: A full manic episode that emerges during antidepressant treatment (e.g., medication, electroconvulsive therapy) but persists at fully syndromal level beyond the physiological effect of that treatment is sufficient evidence for a manic episode and therefore a bipolar I diagnosis.

In my opinion, Mania can look a lot light some forms of PMDD (Pre-menstrual Dysphoric Disorder), where a person has poor cognitive function, high event reactivity, dysregulated mood and frenetic urgency to do certain behaviours.

Most doctors and psychiatrists are not taught what PMDD can look like, so don’t check to see if the female presenting person is experiencing these manic symptoms at certain points in their menstrual cycle.

Hypomanic / Hypomania

Hypomania is a mild form of mania.

To be considered hypomania, the mood must last at least four consecutive days and be present most of the day, almost every day.

From the DSM definition of Hypomania re Bipolar

A distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased activity or energy, lasting at least 4 consecutive days and present most of the day, nearly every day.

During the period of mood disturbance and increased energy or activity, three (or more) of the following symptoms have persisted (four if the mood is only irritable), represent a noticeable change from usual behavior, and have been present to a significant degree:
1. inflated self-esteem or grandiosity
2. decreased need for sleep (e.g., feels rested after only 3 hours of sleep)
3. more talkative than usual or pressure to keep talking
4. flight of ideas or subjective experience that thoughts are racing
5. distractibility (i.e., attention too easily drawn to unimportant or irrelevant external stimuli), as reported or observed.
6. increase in goal-directed activity (at work, at school, or sexually) or psychomotor agitation
7. excessive involvement in activities that have a high potential for painful consequences (e.g., engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments).

The episode is associated with an unequivocal change in functioning that is uncharacteristic of the person when not symptomatic. The disturbance in mood and the change in functioning are observable by others. The episode is not severe enough to cause marked impairment in social or occupational functioning or to necessitate hospitalization. If there are psychotic features, the episode is, by definition, manic.

The episode is not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication or other treatment).

Note: A full hypomanic episode that emerges during antidepressant treatment (e.g., medication, electroconvulsive therapy) but persists at a fully syndromal level beyond the physiological effect of that treatment is sufficient evidence for a hypomanic episode diagnosis. However, caution is indicated so that one or two symptoms (particularly increased irritability, edginess, or agitation following antidepressant use) are not taken as sufficient for diagnosis of a hypomanic episode, nor necessarily indicative or a bipolar diathesis.

In my opinion, it is far too easy to mistake this for ADHD Hyperactivity. Most psychiatrists are taught how to diagnose Bipolar and have the authority to do so, and write scripts for medication for Bipolar. Psychiatrists have to specialise in ADHD to recognise ADHD traits, diagnose ADHD and write scripts for Tier 1 and 2 ADHD medication.

If the tool you have is a hammer, most problems start to look like nails. If you only know how to recognise Hypomania as part of a Bipolar diagnosis, then ADHD Hyperactivity looks a lot like Bipolar Hypomania..

Major Depressive Episode

The technical criteria for Depressive Disorder is the same for most diagnoses that include a “depressed” trait.

For Bipolar, a person must experience five or more of the following symptoms in two weeks to be diagnosed with a major depressive episode.

From the DSM definition of Depressive Disorders

Five or more of the following A Criteria (at least one includes A1 or A2)
A1 Depressed mood—indicated by subjective report or observation by others (in children and adolescents, can be irritable mood).
A2 Loss of interest or pleasure in almost all activities—indicated by subjective report or observation by others.
A3 Significant (more than 5 percent in a month) unintentional weight loss/gain or decrease/increase in appetite (in children, failure to make expected weight gains).
A4 Sleep disturbance (insomnia or hypersomnia).
A5 Psychomotor changes (agitation or retardation) severe enough to be observable by others.
A6 Tiredness, fatigue, or low energy, or decreased efficiency with which routine tasks are completed.
A7 A sense of worthlessness or excessive, inappropriate, or delusional guilt (not merely self-reproach or guilt about being sick).
A8 Impaired ability to think, concentrate, or make decisions—indicated by subjective report or observation by others.
A9 Recurrent thoughts of death (not just fear of dying), suicidal ideation, or suicide attempts.

The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

The symptoms are not due to the direct physiological effects of a substance (e.g., drug abuse, a prescribed medication’s side effects) or a medical condition (e.g., hypothyroidism).

The symptoms are not better accounted for by bereavement (i.e., after the loss of a loved one, the symptoms persist for longer than 2 months or are characterized by marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation).

The criteria for Major Depressive Disorder is identical to the above, but it also disallows for mania or hypomania, or another condition such as schizophrenia or psychosis – effectively that is the main difference between Bipolar Depression and MDD – a manic episode (thus Bipolar 1) or hypomanic episode (thus Bipolar 2).

In my opinion, there are quite a few other conditions that will tick enough boxes for this criterium to be met, but are not Bipolar, MDD, schizophrenia spectrum or psychosis.

There are diagnostic forms that help a therapist to decide if a person meets the criteria for one of the forms of Bipolar.

Cyclothymic Disorder

Cyclothymic Disorder is diagnosed when an individual experiences, for at least two years (or one year for children and adolescents), periods of elevated mood and depressive symptoms that do not meet the criteria for a hypomanic or major depressive episode, respectively.

These mood shifts are accompanied by periods of stable mood that last for no more than two months.

Due to the nature of the fuzzy definition of “elevated levels of mood and depressive symptoms” for “at least 2 years (for adults)” accompanied by “periods of stable mood”, this soft Bipolar diagnosis is likely to lead to a misdiagnosis.

Common Bipolar Medical Treatments, and what they tell about your Bipolar

The most common medication categories for Bipolar are

  • Antiepileptic mood stabilisers
  • Antipsychotics
  • SSRI class antidepressants

Other medications can work that aren’t listed here – take a look further down about Bipolar and Hormones.

Antiepileptic Mood Stabilisers

Antiepileptic medication typically slows down the signal speed and strength between neurons. This seems to have a moderating effect on mood, which can have them also referred to as mood stabilisers. Many of them seem to affect the adrenaline system and or the cell mitochondria.

Generally, if this works for your bipolar symptoms, stabilising your moods and giving you sufficient cognitive function to have a good quality of life, then you likely have been diagnosed correctly with Bipolar.

The most common Antiepileptic medications given to Bipolar are: [click on “>” to expand]

Lithium Salts (use with care)

In my opinion, if you find that Lithium Salts medication helps you feel regulated and functional, then you are mostly likely to have Bipolar. In my experience, when Lithium Salts just work when nothing else does, then we are very likely not dealing with a misdiagnosis.

We don’t really know why it works. What we do know is that soon after taking Lithium, it spreads throughout your central nervous system, decreasing noradrenaline release (read below regarding BPAD, Hormones, ADHD and PMDD) and increasing the production of Serotonin.

There are some interesting speculations about how Lithium affects the action of the cells mitochondria and how that may lead to helping BPAD [“Lithium and the Interplay Between Telomeres and Mitochondria in Bipolar Disorder”, 2020].

Caution: Lithium, as a medication, has a host of things that can go wrong, and should be closely monitored for Lithium Toxicity (where the levels of Lithium exceed your bodies ability to manage them), and hyperthyroidism / hypothyroidism (most opinion is that Lithium can cause the over or under activity of the thyroid, however, some BPAD has been linked to thyroid issues prior to Lithium… so which came first, or is it both?) and a few other important considerations.

Valproate

In my opinion, if Valproate medication helps you feel regulated and functional, then you are mostly likely to have Bipolar. In my experience, when Valproate just work when nothing else but Lithium does, then we are very likely not dealing with a misdiagnosis. Valproate is safer to use than Lithium, but not quite as effective.

Valproate is often used when Lithium either can no longer be tolerated, or if the patient rejects trying Lithium due to its risks. Valproate is often also commonly prescribed for epilepsy, sometimes for migraines if other medication isn’t effective, for schizophrenia when antipsychotics aren’t effective, and occasionally to treat dopamine dysregulation syndrome in responses to Parkinson’s disease medication.

How Valproate works is not well understood. Neurologically, it inhibits the signal speed between neurons by acting as a voltage-gated sodium channel blockade and increases the levels of GABA (which can offset overactive dopamine, noradrenaline and adrenaline). Valproate also acts as an antagonist of the androgen and progesterone receptors effectively decreasing their effect, and suppresses oestrogen concentrations. Valproate also, like Lithium above, seems to affect the mitochondria.

Lamotrigine (caution)

Lamotrigine is primarily prescribed for epilepsy and bipolar.

The studies on the effectiveness of Lamotrigine for Bipolar show that it is highly variable, with some claiming it works as well as Lithium Salts, some claiming that it is good as an antimanic agent, others stating it is not; some stating it is good for the depression symptoms, other stating it is not; and so I contest that Lamotrigine is not actually a good starting place for treating Bipolar [Read more].

In my experience, Lamotrigine is rarely the right medication, but when it is – it is really good.

Lamotrigine is a sodium channel blocker, which slows down the signal speed and strength between neurons. It likely supresses glutamate and aspartate, important neurotransmitters for the excitation of the central nervous system. It is considered more effective for Bipolar than many other sodium channel blockers, and this is likely due to Lamotrigine having a broader effect than just sodium channel blocking.

Lamotrigine also blocks calcium channels, further slowing thought, and weakly inhibits the serotonin 5-HT3 receptor, which can have an antidepressant effect [Read more], mostly via affecting GABAergic mechanisms [Read more]. Lamotrigine has a weak reuptake inhibition of Dopamine and Noradrenaline, often key aspects in medication for ADHD.

Caution: Lamotrigine has a black box warning regarding life threatening skin reactions. “Women” often have stronger side effects to Lamotrigine than “men”, and this is thought to be around how it interacts with estradiol, especially in contraceptives. While Lamotrigine affects DHFR, which would normally lead to birth defects such as cleft palates, however no study has shown that Lamotrigine causes more defects than in the background population.

In my experience, when Lamotrigine is not right for you, you’ll experience nausea, confusion, mood dysregulation and higher than normal ideation.

These medications are fairly serious medications with potentially quite serious side effects or consequences. While Lithium and Valproate are mostly the only medications that work on what I consider to be “true Bipolar”, you’ll want to check that your mood disorder actually is Bipolar and not another mood related condition. We cover that in Bipolar and Hormones.

Antipsychotics

Antipsychotics primarily block a Dopamine Receptor called D2, which is linked to psychosis. Older Antipsychotics will block most of the 5 types of Dopamine receptors, while newer Atypical Antipsychotics will block 2 or 3 of the Dopamine Receptors – where one of those is always D2. Most of the blocking of the receptor is in the prefrontal cortex, where you do most of your higher order thinking (Executive Function). We discuss a bit more about this in the Dopaminergic System page.

By blocking the receptor, the Dopamine molecule can’t trigger the receptor and the signal is not passed through. This can be particularly problematic for people diagnosed with ADHD.

Antipsychotics often affect other areas of the brain, decreasing the arousal system and effectively acting as a sedative. Often Antipsychotics are given to people diagnosed with Bipolar to hold back the mania behaviours. It does not seem to help the more common depressive symptoms, and it does not seem to stop the peak manic episodes either.

In my opinion, if an antipsychotic is the sole medication you have been prescribed for Bipolar:

  • It is worth asking your doctor to trial Clonidine during your manic phase and see if it helps.
    • If it does, you likely have a noradrenaline regulating problem and not Bipolar
  • If you find that the antipsychotic is generally poorly effective:
    • Then either consider trialling Lithium (if medically safe to do so, ask your psychiatrist).
    • Check to see if your diagnosis is correct (rather, if another diagnosis is a better fit, like ADHD).
  • If your antipsychotic is generally doing a good job:
    • Don’t change it.
    • It is still worth checking to see if Bipolar is the correct diagnosis.
      • It might be and one of the non Dopamine Receptor effects of the medication is successfully treating the Bipolar disorder

SSRI Antidepressants

SSRI stands for Select Serotonin Reuptake Inhibitor. They are supposed to only affect Serotonin expression and Serotonin receptors, but almost none of them do that (affect only Serotonin). The exception to this is Citalopram, which mostly only targets Serotonin. Reuptake inhibition is poorly understood, however the upshot of it is that the targeted neurotransmitter works more efficiently, thus the same amount goes for longer.

Neurological Serotonin’s function is poorly understood. Despite many papers claim that it effectively does everything, it doesn’t. What it does seem to do is:

  • Counter balance the Dopaminergic sympathetic arousal.
    • Slow down over reactivity.
    • Give you a moment to think before you act.
  • Help run the resource allocation system.
    • If you are low on a neurotransmitter, it prompts for more of that neurotransmitter; if you are high in that neurotransmitter, it prompts for less production.
    • It does not help the core problems of conditions like ADHD, Schizophrenia or Parkinson’s Disease, where the brain thinks that the “right amount” of production is not workable.

SSRI medications for Bipolar rely on the mechanisms of the “SSRI” on non-Serotonin connections and levels in the brain.

If you have an SSRI that is helping your Bipolar, you likely don’t have Bipolar, you have another condition. Take a look at what other neuronal effects that particular medication has, such as Dopamine and Noradrenaline. This will give you a better clue about what may be really going on.

Bipolar and Hormones

Bipolar Affective Disorder is supposed to have no biological sex distinction – that is, it should be just as common with cis males as it is with cis females [cis means the person identifies as the same gender as what their biology at birth suggests]. Despite this expectation, we find that around 80% of people diagnosed with Bipolar Affective Disorder are female.

Growing evidence shows that BPAD is not only more commonly diagnosed in women, but Major Depressive Disorder is frequently attributed to women, where the diagnostic criteria indicate that the better diagnosis should probably have been BPAD.

If Bipolar is diagnosed more in women, is this hormone related?

Likely Yes:

Bipolar, Hormones, ADHD and PMDD

One of the forms of ADHD is that Dopamine is too quickly converted to Noradrenaline. This results in low cognitive function due to the low Dopamine and agitated and hypervigilant due to this excess Noradrenaline (the too much re the Goldilocks Zone).

Oestradiol is a key sex hormone in both the menstrual cycle and in the production of Dopaminergic neurotransmitters – Dopamine, Noradrenaline and Adrenaline.

Dopamine is the main neurotransmitter used to help us think, understand, predict, solve and recall information in a complex process called the Executive Function.

Noradrenaline is the main neurotransmitter we use to assess if we are “safe” or “not safe” and thus our mood and priorities.

Adrenaline is the main neurotransmitter that initiates and completes tasks, physical actions and manage crises.

Oestradiol is the sex hormone that directly regulates how much Dopamine, Noradrenaline and Adrenaline we synthesise in our brain. Low Oestradiol means low Dopamine etc. This can stack with ADHD, a condition that often has lower Dopamine production, leading to problems with the Dopaminergic Neurotransmitter levels, and often this causes PMDD (Pre-Menstrual Dysphoric Disorder).

The amount of Oestradiol varies during your menstrual cycle, as represented by the grey line in the following graph.

Bipolar 1 ADHD/ PMDD Variant

For these ADHDers, in the peak Oestradiol phase of their menstrual cycle, they may be synthesising normally good quantity of Dopamine, but they are quick converting too much of the Dopamine to Noradrenaline, flooding the Amygdala. This leads to cognitive confusion and hyperactivity. The high Oestrogen and Progesterone can trigger a euphoric feeling that channels the feeling from the Amygdala to over the top behaviours, extreme happiness, and thus odd behaviours.

Again, for these ADHDers, during the trough PMT phase, they will make only a little Dopamine, which can’t be converted easily into Noradrenaline, which leads to low production of Adrenaline. This leaves you feeling cognitively confused, sad, depressed and absent of any energy to do any tasks.

During that lowest phase, the PMT section just prior to menses (menstrual flow), if you often find it hard to think, you are disassociated, significantly mood dysregulated and experiencing odd behaviours, then you may be experiencing PMDD. You may also find a small depression or odd mood just after ovulation for 1 to 2 days, which I call the Mid Cycle Crash. We also discuss that on the main PMDD page.

As the Menstrual Cycle is … a cycle, this then leads to high and low cycling, which can look like Bipolar.

Bipolar 2 ADHD/ PMDD Variant

Some people have naturally lower Oestrogen throughout their cycle, leading to symptoms of Depressive Disorder for the majority of the menstrual cycle and some feelings of “okay” during the peak Oestradiol phases (pre and post ovulation). Occasionally, your cycle may produce enough Oestradiol to feel good, perhaps even hyperactive, often mistaken for hypomania.

To test this hypothesis, I recommend my clients to get a few hormone blood tests (specifically Oestradiol) during different parts of their cycle.

  • First blood test should be on the first day of menses (menstrual flow).
    • We call this “day 1” of the menstrual cycle.
    • This should be your lowest Oestradiol level (or close enough).
    • Ideally this level should be 300+ pg/mL.
      • Some people are fine with 200, but that isn’t common, and if you are matching symptoms of Depressive Disorder mostly around this time, this may be why.
  • The second blood test should be around day 12.
    • That is, 12 days after you started your cycle, or around 5 to 8 days after your menstrual flow stopped.
      • This is assuming you have a regular 28 day menstrual cycle. If you have a longer or shorter regular cycle, then do some math to work out a day prior to the middle of yours.
      • If you have an irregular menstrual cycle, then the day you feel quite good 4 or more days after you finish menses is close-ish.
      • This should be a day that you feel good, or at least, much less bad.
    • On average, this part of your cycle is when your Oestradiol is at its peak (see the chart above).
    • If your Oestradiol is between 1000 pg/mL and 1800 pg/mL, then your peak Oestradiol hormone should be fine and you should feel good and be functional.
      • If you aren’t feeling good and functional, something else is likely causing that.
    • If your Oestradiol is lower than 600 pg/mL, this may be why you are struggling.
      • You may want to consider adding hormones.
      • The easiest way for most people to do this is ask your doctor for contraception that includes Oestradiol. Typically this comes with Progesterone.
  • A third blood test may be useful if / when you experience mania like symptoms.
    • If your Oestradiol is over 2000 pg/mL, this may be why you are manic / hyperactive.
      • Ask your GP for a referral to a sex hormone endocrinologist.
      • Get your thyroid function checked, as this can cause all of this (rare, but it happens).
      • Talk to your endocrinologist about Oestrogen modulators.

Tamoxifen is a selective Oestrogen receptor modulator; a modulator is a medication that props up low levels of a biochemical and suppresses high levels of that biochemical (this is simplified). That means that Oestrogen won’t go too low, and neither will it go too high. Tamoxifen is not currently listed as a medication for BPAD or MDD in Australia. It is usually used as a preventative for breast cancer.

A Final Word on Bipolar

  • Oestrogen isn’t the cause for Bipolar in all women.
    • If your Bipolar is treated by Lithium medication, then likely this won’t work.
    • The research into Oestrogen modification for Bipolar is still young.
  • Not all Bipolar is actually ADHD or PMDD.
    • A way to test this is if a neuronal Noradrenaline suppressant like Clonidine drops your manic phase back to normal.
    • If it does, then this is probably PMDD.
    • If it doesn’t, then likely it is the typical Bipolar.