Bipolar disorder is a chronic condition that requires long-term management, often with mood-stabilizing medications. However, the use of these medications during pregnancy presents a challenge due to the potential risks to the developing fetus.

One such medication, sodium valproate, is associated with a significantly higher risk of neural tube defects (NTDs) and other developmental issues. The baseline risk of NTDs in the general population is approximately 1 in 1000 (0.1%). However, the use of valproate during pregnancy increases this risk significantly, with studies showing that approximately 1 to 2 in 100 babies (1%-2%) born to women taking valproate in pregnancy will have an NTD (Tomson et al., 2018).

Women with bipolar disorder who wish to become pregnant often need to consider alternative medications. Two often-considered alternatives are lamotrigine and lithium.

Lamotrigine (Lamictal)

Lamotrigine has been increasingly used during pregnancy due to its lower teratogenic risk profile compared to other mood stabilizers. However, some studies suggest a small increased risk of oral clefts with lamotrigine exposure in utero. A meta-analysis by Meador et al. (2018) indicated a prevalence rate of oral clefts of 0.27% (27 per 10,000) with lamotrigine use in the first trimester, which is slightly higher than the baseline risk in the general population (about 10 per 10,000).

Despite this small increase, lamotrigine is often considered one of the safer mood-stabilizing drugs for use during pregnancy due to the overall lower risk of major congenital malformations (Meador et al., 2018).

Lithium

Lithium, a first-line treatment for bipolar disorder, is also an option during pregnancy. However, it has been associated with an increased risk of cardiac malformations, specifically Ebstein’s anomaly, a rare heart defect. The baseline risk of Ebstein’s anomaly in the general population is approximately 1 in 20,000 (0.005%) (Medsafe, 2018). Research indicates that lithium exposure during the first trimester may increase this risk to around 1 in 1,000 to 2,000 (0.05%-0.1%) (Medsafe, 2018; Patorno et al., 2017).

While this represents a significant relative increase, the absolute risk remains small. The benefits of lithium, particularly for individuals with a history of severe manic episodes, often outweigh the potential risks.

Antipsychotics

Atypical antipsychotics such as olanzapine, quetiapine, or lurasidone are also considered for use during pregnancy, though their safety profiles are not as well established as those of lamotrigine and lithium (Gentile, 2017).

Efficacy in Treating and Preventing Mania/Hypomania

In addition to the safety profiles of mood stabilizers during pregnancy, it’s also important to consider the efficacy of these medications in managing bipolar disorder and preventing relapses of mania or hypomania.

Sodium Valproate: Valproate is a highly effective mood stabilizer, and it’s particularly potent in treating and preventing manic episodes. However, as previously discussed, its use during pregnancy is associated with significant risks to the fetus, leading many clinicians to avoid its use in women of childbearing age when other effective alternatives are available.

Lamotrigine: Lamotrigine is considered effective in managing bipolar disorder, particularly in the prevention of depressive episodes. Its efficacy in preventing manic episodes is considered less robust than that of lithium or valproate, but it can still be effective, especially in combination with other treatments.

Lithium: Lithium is a first-line treatment for bipolar disorder, and it’s particularly effective at preventing manic relapses. Its use during pregnancy is associated with a small increased risk of cardiac malformations, but for many women, the benefits in terms of mood stabilization may outweigh the risks.

Atypical Antipsychotics: Several atypical antipsychotics, including olanzapine, quetiapine, and lurasidone, have been shown to be effective in treating acute mania and in maintenance treatment to prevent relapse. Their safety profiles during pregnancy are not as well established as those of lamotrigine and lithium, but they can be considered when other treatments are not suitable or effective.

Conclusion

Changing medications should always be done under the close supervision of a psychiatrist, and the patient should be stable on the new medication before attempting to conceive. Additionally, it’s crucial to involve an obstetrician who specializes in high-risk pregnancies. Folic acid supplementation is recommended for all women of childbearing age, but particularly for those on antiepileptic drugs, to reduce the risk of neural tube defects.

While these are general recommendations, each patient’s case is unique and should be managed individually, considering their unique medical history and circumstances.

References

Gentile, S. (2017). Antipsychotic therapy during early and late pregnancy. A systematic review. Schizophrenia bulletin, 43(4), 752-761.

Meador, K. J., Baker, G. A., Browning, N., Clayton-Smith, J., Combs-Cantrell, D. T., Cohen, M., … & Kalayjian, L. A. (2018). Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study. The Lancet Neurology, 12(3), 244-252.

Tomson, T., Battino, D., Bonizzoni, E., Craig, J., Lindhout, D., Sabers, A., … & EURAP study group. (2018). Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry. The Lancet Neurology, 17(6), 530-540.

Medsafe. (2018). Prescriber Update 39(4): 50-56. Retrieved from: https://www.medsafe.govt.nz/profs/PUArticles/December2018/MedicinesUseInPregnancy.htm

Patorno, E., Huybrechts, K. F., Bateman, B. T., Cohen, J. M., Desai, R. J., Mogun, H., … & Hernandez-Diaz, S. (2017). Lithium use in pregnancy and the risk of cardiac malformations. The New England journal of medicine, 376(23), 2245-2254.

Yatham, L. N., Kennedy, S. H., Parikh, S. V., Schaffer, A., Bond, D. J., Frey, B. N., … & Sharma, V. (2018). Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar disorders, 20(2), 97-170.

National Collaborating Centre for Mental Health (UK). (2014). Bipolar disorder: the assessment and management of bipolar disorder in adults, children and young people in primary and secondary care. Leicester (UK): British Psychological Society.

What is a burnout? What are its symptoms? Is it considered a mental illness?

“Burnout” was coined in the 70s by psychologist, Herbert Freudenberger. To date there is no scientific definition for burnout. It is general description of loss of interest and motivation towards work, following a long period of excessive stress. The sufferer complains of tiredness and lethargy. He or she may feel unappreciated and may be cynical about work and colleagues.

Read about the differences between Burnout and Depression here.

Why are medical professionals more susceptible to suffering from burnout? What do you think are the factors that cause doctors to feel burnt out?

The nature of the work encountered by medical professionals make them more susceptible to burnout. Diseases go on for 24/7 and do not respect office hours. Medical professionals often have to work long hours, rotate through shifts and attend to patients on weekends. Some may continue to worry about the patients they are in charge of even during after hours. Due to the long hours and shifts, they may not have time with their family and friends, to attend to their hobbies, or to even rest.

Medical professionals also have to face crises, deaths and sicknesses all the time. The emotional aspects of the work can be daunting and draining.

Finally, little is done to address burnout in medical professionals within the fraternity. We are expected to be able to handle long work hours and traumatic experiences even as junior doctors. An inability to cope is seen as a weakness and as such medical professionals are often fearful and unwilling to speak up when stressed up or to seek help.

How could burn out affect doctors as well as their work?

As doctors get burnt out, they will start to feel easily exhausted, and start to lose interest and confidence in their work. They may become easily tired and irritable at work. Some may start having anxiety during the weekend about the start of the work week. They may find it hard to drag themselves out of bed each and every day. When the burnout worsens. these difficulties may spread to their social and family life. They may lose their temper easily with their partners, spouses or children. In extreme cases, an anxiety disorder or clinical depression may ensue.

Can you share more about your experience as a doctor? What were some of the difficulties and challenges you faced that were not so apparent to non medical workers or non-doctors?

Doctors are deemed to be in a privileged position by society. In Singapore, the medical fraternity holds it upon ourselves to have high regards to ethics and to our fiduciary duty to our patients and society. In this regard, being a doctor does not end when we leave the hospital or the clinic as one must continue observing the decorum befitting of the profession. We are also very conscious of this in our work and the obsession over being careful all the time can be very tiring.

The doctor patient relationship can also be a tricky one. The doctor-patient relationship is seen to be sacred by us. We have to be personable and approachable but at the same time maintain a boundary with patients. We have to be mindful that our treatment decisions must at the same time be for the patients’ best interest, uphold social justice and evidenced based. Many a times, a recommended treatment may not be what the patient wants and this can often result in unhappy encounters for both sides. For eg. a patient may feel that he deserve a longer medical leave but his condition does not justify it and doing so will be unfair to his company and his colleagues.

While we may work in a team in hospitals, most of the time, we have to make clinical decisions, some of which are life or death situations, independently on our own. Not all good decisions lead to good outcomes but it is still hard to shake the guilt off when outcomes are negative, even when we tried our best.

Have you or any colleagues suffer from burn out? How did you/they cope with it? How can fellow doctors or their loved ones help them?

it is not uncommon to see colleagues suffer from some form of burn out after which they may leave their job or give up some responsibilities. Personally, while I have not experience overt burn out, I have in the past become rather irritable when I am overworked.

It is therefore important for doctors to be aware that we are not infallible and to also be mindful of our psychological wellness or the lack of. Rest is the most effective remedy for burn out and having proper sleep, exercise and hobbies are important. We should ring fence our time and have a break from work, so that we have time to do so.

Doctors do get together in informal support group to rant and ventilate about work. Talking it out helps a lot. Family members and loved ones can also be emphatic, patient and provide listening ears.

When should medical professionals seek treatment for burn out problems?

Prevention is always better than cure. Having adequate rest and a proper work life balance are essential in preventing burn out and making it possible to sustain our work as doctors.

However, when a medical professional start noticing he is having symptoms of burnout and becoming less effective at work, he should start taking steps to slow down his pace. If he notice that he is starting to have excessive anxiety, prolonged low mood, difficulties with sleep and appetite, inability to discharge his duties as a doctor, or even suicidal thoughts, he should seek treatment.

Like Depression, Anxiety Disorders occurs commonly in the general population. Studies have shown that as high as one in six people will suffer from an episode of an Anxiety Disorder once in their lifetime.

Anxiety disorder refers to the following psychiatric conditions:

1. Generalised Anxiety Disorder (GAD)
2. Panic Disorder
3. Post Traumatic Stress Disorder
4. Social Anxiety
5. Obsessive Compulsive Disorder
6. Phobias

Whilst many people who suffer from anxiety may concurrently have depression as well, this is not always the case. Antidepressant medications have a wide spectrum of activity and are effective in the treatment of anxiety, pain disorders, ADHD and other psychiatric disorders. These medications are called antidepressants as they were first developed and used in the treatment of depression. Therefore, having been prescribed an antidepressant does not mean that you are suffering from depression in any way.

The classes of antidepressants include:

1) Selective Serotonin Reuptake Inhibitors, eg. Escitalopram, Setraline, Fluoxetine, etc
2) Serotonin and Noradrenaline Reuptake Inhibitors eg. Duloxetine, Venlafaxine
3) Tricyclics Antidepressants, eg. Amitriptylline, Clomipramine

The type of antidepressants used depends on the type of symptoms you are experiencing, previous use of antidepressants and the side effects profile of these medications. Antidepressants can cause side effects in about 5% of people who taken them. These side effects are short term and reversible. I will discuss them in another article as users are often worried about side effects and they warrant a full article to debunk many of the fears related to them.

It is important to note that antidepressants usually take about one to two weeks to start working and their effects are gradual. As such some use of tranquillisers may be needed in the short term.

Tranquillisers

Minor tranquillisers like benzodiazepines (eg. alprazolam and lorazepam) will help to ease anxiety quickly. However, they can potentially cause dependency issues if abused and have to be given judiciously and mostly only during the start of treatment while we are allowing the antidepressants to take effect. Very low doses of major tranquillisers like Quetiapine and Risperidone may be used sometimes to help manage the anxiety. It is important to remember that the mainstay of treatment is still antidepressants and tranquillisers are for short term use.

Safety of Medications

From extensive research and experience, the medications used in anxiety disorders are safe when used as directed. Side effects are short lived and at best troublesome.

Other Treatments 

Various forms of therapy are also useful with Anxiety Disorders. They can be considered as first line when the anxiety is mild or they can be used in conjunction with medications. Some patients do find it hard to initiate therapy and to follow through with the home work of challenging their negative thoughts when they are anxious and may need a period of stabilisation with medication before therapy can be commenced.

Duration of Treatment

Many worry that they will need to take medications forever once started. This is a misconception. Many people with anxiety disorder suffers only one episode. The medications will ease the symptoms and with time (depending on their condition) they will come off medications. However, if you have had many episodes of anxiety disorders, if may be beneficial for you to stay on medications on a longer term.

Pharmacogenomics can be understood as the science of how genes interact with medication in a person’s body to affect its response. We know that every individual is different and would respond differently when given the same medication. Some may need a higher dose. Some may need medication of a different mechanism. In the past, we are not able to determine who will need what and medication treatment is often a one size fit all or even carpet bombing approach. The lack of predictability to side effects, and effective doses often leave doctors blind sided and frustrated.

Today, we know that our genes play a big part in how our body interacts with drugs. A major system is the cytochrome P-450 (CYP) family of enzymes which metabolizes drugs in the liver. To put it simply, the presence of genetic differences (what we call allelic variants / polymorphisms ) in the CYP enzymes result in three main phenotypes (observable characteristics), i. e. poor metabolizers (PMs), normal metabolizers (NMs), and extensive metabolizers (EMs). This results in some people having more side effects with certain medications and can account for some of the reasons why some people need higher or lower doses of medication.

Using clinical depression as an example, there may be individuals who have major gene-drug interaction. An increase in the metabolism due to the genotype (genes) may decrease the patient’s exposure to the medication, necessitating a higher dose. An inadequate dose may result in treatment failure or mimic treatment resistance. Conversely an decrease in metabolism may increase exposure to medication resulting in more side effects like diarrhoea or nausea.

Now that pharmacogenomic testing is available, we can now piece in this missing part of the jigsaw. Testing for certain polymorphisms / genetic differences before prescribing certain drugs can help avoid adverse drug effects and improve efficacy.