Bipolar Medications and their Side Effects

Image by Emilian Danaila from Pixabay 

First published in Bipolar Life's April 2020 newsletter

INTRODUCTION

Most people living with bipolar disorder understand the importance of medication in the management of their condition. We know that medications are to be taken lifelong, with a few exceptions. We also understand that they are taken in addition to, not as a replacement for, other treatments such as psychotherapy, healthy lifestyle and a good routine; this includes a good sleep pattern, regular exercise, good nutrition and strong social support.

So, what happens if we don’t treat bipolar disorder in the right way, for instance self-treating? The following scenarios could happen [1]:

• More frequent and severe mood episodes
• Damaged relationships
• Loss of job or damaged career
• Money problems
• Problems with thinking and memory

Therefore, it makes sense for you to work with your doctor to ensure the medications prescribed are right for you. As all medications can cause side effects, it is essential to be open and honest with your prescribing doctor if you are experiencing any problems. It is inadvisable to reduce or stop a medication without consulting with your doctor first.
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In this article we are going to look at:

• the possible side effects of the most commonly used medications
• medication interactions with illicit drugs/alcohol
• regular monitoring as a way of reducing medication problems
• coping strategies for less severe issues, and
• what to do if you feel you cannot continue the medication

Bipolar disorder is treated with three main classes of medication: mood stabilisers, antipsychotics and antidepressants. Sometimes your doctor may prescribe (usually short term) anti-anxiety and sleep aids–benzodiazepines and Z drugs. In this article we won’t go into much detail how they are used, such as acute treatment versus maintenance, or what is used for mania versus depression. Instead we’ll just concentrate on the side effects aspect to keep the article reasonably short.

MOOD STABILISERS – LITHIUM [1,5]

​Around 75% of people of people taking lithium for bipolar disorder get side effects [2]. It is effective for mania, and is gold standard for maintenance therapy, and may help bipolar depression [1].

Important note on lithium toxicity

This can be caused by various factors such as taking too many tablets, dehydration, or having a sudden drop in kidney function. This can be a dangerous condition and needs urgent medical attention. Symptoms can include nausea, vomiting, diarrhoea, drowsiness, unsteadiness, confusion, agitation, blurred vision, severe tremors, muscle jerks or seizures [4].

People taking lithium are recommended to have regular blood tests to check lithium levels, kidney and thyroid function [5].

How to avoid dehydration
​
To avoid dehydration, it’s important to keep well hydrated especially if exercising, or in hot weather. Try not to have too much caffeine or alcohol as they can dehydrate. Medications such as diuretics and non-steroidal anti-inflammatory drugs (such as ibuprofen) can also cause lithium levels to rise so care is needed.
 
We’ll now look at the anticonvulsants which are also used as mood stabilisers.

MOOD STABILISERS – ANTICONVULSANTS [1,6]

Important note on Stevens-Johnson syndrome

This is a rare, serious disorder of the skin and mucous membranes. It usually begins with flu-like symptoms (such as fever, fatigue, cough), then a red or purplish blistering rash that spreads over the body. The mouth, eyes, nose and genitals can be affected [7]. You must seek immediate medical attention if you suspect you are having this reaction to a medication.

ANTIPSYCHOTICS [1,8]

The first antipsychotics developed, now known as first-generation typical antipsychotics (FGA), were used to treat people with schizophrenia in the 1950s. The second-generation antipsychotics (SGA) came out in the 1980s, and are commonly known as atypical antipsychotics [9]. The SGAs are helpful in reducing mania and in strengthening antidepressant treatment [1].

The SGAs generally are far less likely to cause a particular class of side effects, the extrapyramidal side effects such as restlessness, muscle stiffness, involuntary neck spasm, Parkinson’s like movements, involuntary facial and mouth movements [10].

It is recommended that people taking antipsychotics should have 6-12 monthly monitoring to check weight, blood pressure, fasting glucose and cholesterol, and ECG (heart trace) [11].

ANTIDEPRESSANTS [1,12]

Treating depression in someone with bipolar disorder is less straightforward than for unipolar depression. For instance, in type 1 bipolar, antidepressants may be less effective [1]. Also, mania can be triggered by use of an antidepressant, particularly if the person is not also taking a mood stabiliser. There are several classes of antidepressant. Some of their brain actions are similar, some are different, and this is reflected in the differing side effect profiles in the table below.

There are some less commonly used antidepressants available in Australia. These include mirtazapine, trazodone, the Tricyclic Antidepressants (TCAs, such as amitriptyline and nortriptyline) and MAOIs (monoamine oxidase inhibitors such as phenelzine and tranylcypromine). You can read more about TCAs here [15] and MAOIs here [16].

​ANTI-ANXIETY AND SLEEP MEDICATIONS

Anti-anxiety medications (anxiolytics) and sleep aids (hypnotics) can be immensely helpful in the acute phase of depression and mania treatment. These are generally within the class of benzodiazepines (such as diazepam, temazepam, lorazepam) or Z drugs (such as zopiclone, zolpidem).

Both benzodiazepines (“benzos” for short) and Z drugs pose a risk of dependence, so these medications are usually prescribed for as short a time as possible. Some people do require them longer term, but this requires strict monitoring by their doctor.

Side effects can range from mild to severe. This can include daytime sedation, or impaired ability to drive, operate machinery or perform certain tasks.

In overdose, or if taken with certain other drugs (prescribed, over-the-counter or illicit), or alcohol, adverse effects can be severe and even result in coma or death. The elderly are also at particular risk from these medications.

It is possible to become dependent after just a few weeks of taking them regularly [17]. Signs of this process happening include:

• a strong psychological or physical need to keep taking the medication even when the initial symptoms have disappeared
• a need to take higher doses to achieve the same effect (this is known as tolerance)
• anxiety, panic attacks, feeling spaced out, insomnia, sweating, tremor, nausea, palpitations, headaches, over-sensitivity to light/sound/touch, or weakness [18,19]

Withdrawal from benzos needs to be done with regular review by your doctor. Some people can feel unwell if reducing too quickly, and may experience agitation, insomnia, hallucinations and seizures [17].

​WHO MIGHT BE AT INCREASED RISK FOR SIDE EFFECTS?

Older people are less able to metabolise their medications through the kidney and liver. At any age, but often more commonly seen in the elderly, being on a cocktail of medications can increase the risk for drug interactions and adverse effects. This is an important issue that needs regular monitoring by their doctor [20].

People who have pre-existing medical conditions may find them aggravated by weight gain, increased glucose or cholesterol. These conditions include high blood pressure, heart disease, history of stroke, diabetes, liver disease, kidney disease and arthritis.

Substance use disorder can be seen in one-third to one-half of people with bipolar disorder [1]. People who drink alcohol, particularly if in excess of recommended levels, or take illicit drugs, may be at higher risk for side effects–in addition to the drugs and alcohol potentially worsening control of their bipolar disorder. Alcohol may cause dangerous interactions, especially when taken with lithium and benzodiazepines [1]. 

​WHAT TO DO IF YOU ARE EXPERIENCING SIDE EFFECTS

Keeping a journal when you start or change a drug regimen can be helpful in working out if a symptom is really a side effect or whether it is the illness, or something else entirely.
​
If you think you are getting side effects, regardless of whether they are new or longstanding, it is a good idea to check in with your doctor. It might be decided that they side effects are mild and non-serious, and the benefits of the medication outweigh the adverse effects, in which case you could opt to continue.

Possible other scenarios include:

• Your doctor might advise you to wait and see. Some side effects can improve with time, such as the nausea and tremor associated with lithium [3], or the nausea of SSRIs [13].
• Your doctor might advise you that the drug regimen needs changing. That could entail a reduced dose, a change of timing (e.g. night versus morning dosing), or a change to a slow or extended release formulation.
• Your doctor might advise you that the medication should be stopped.
• Your doctor might advise you the medication should be switched to another one, sometimes within the same class.

​TIPS FOR SPECIFIC SIDE EFFECTS

Here are some tips for specific issues. Once again, these are ideas for you to discuss with your doctor first.
 
TREMOR [3]

• Watchful waiting may be sufficient where tremor is mild as it may resolve in time
• Reducing caffeine as this can aggravate tremor
• Changing lithium salt (e.g. from carbonate to citrate)
• Changing lithium from long- to short-acting
• Reducing the daily dose
• Splitting the daily dose
• Adding a beta-blocker to treat the tremor

 
NAUSEA [3]

• Watchful waiting may be sufficient where nausea is mild as it often resolves in time
• Taking medication with or after food
• Taking sustained release rather than fast release formulation
• Reducing the daily dose
• Splitting the daily dose

 
SEDATION [1]

• Taking medication later in the day or before bed
• Taking a short nap during the day if needed
• Taking regular light-moderate exercise such as walking

 
WEIGHT GAIN

• Monitor your weight regularly, say twice a week. This way you can monitor the effects of your efforts with diet and exercise.
• Some people find keeping a food diary helps. This can also help us realise when we are “emotional eating” or eating out of boredom.
• Eating mindfully may help with weight loss. It takes about twenty minutes to feel full, so savour every mouthful. This article [21] explains this in more detail and includes helpful tips on how to eat mindfully.
• Make changes gradually and set realistic, achievable goals. Set yourself up for success! You can read more about SMART goals here.
• A nutritious, portion-controlled diet with adequate exercise is key.
• There are many resources available to support you on your journey. This could include seeing your GP, dietician and/or exercise physiologist. There are also great online resources such as this general guide [22], or this free 12-week weight loss plan [23] produced by the NHS.

 
SEXUAL DYSFUNCTION

• Sexual dysfunction includes problems with libido, arousal or orgasm.
• This side effect is a particularly important one as it can affect relationships, and unfortunately many people may be too embarrassed to report it. One source suggests about half of people taking SSRIs experience this, and that it occurs in the atypical antipsychotics at incidences ranging from 16-27% (aripiprazole) to 50-60% (olanzapine, quetiapine, ziprasidone) to 60-70% (paliperidone, risperidone)24.
• Reducing the dose can help [1].
• Switching medication, sometimes within the same class can help [1].
• Following a drug holiday e.g. not taking the problem medication one day a week, as long as the regime doesn’t affect the bipolar disorder [1].

 
MEMORY AND COGNITIVE ISSUES [3]

• Discuss this with your doctor as it is sometimes tricky to work out whether poor memory or foggy thinking are due to the bipolar disorder or the medication. If related to the bipolar, it may get better in time as the treatment starts to work.
• Lithium-induced cognitive impairment can often lead to people stopping their medication. If someone is also taking antipsychotics, antidepressants or benzodiazepines then the foggy thinking could worsen. Foggy thinking is also thought to be worse at higher doses and may get worse over time.
• If the foggy thinking is due to the medication, your doctor might suggest reducing the dose, splitting the dose and possibly stopping other medications that may be aggravating the issue.
• In addition, timetabling in mental or physical activity to stimulate the brain may be beneficial [1].

 
HAIR LOSS (SODIUM VALPROATE]

• Hair loss is generalised, rather than patchy, and does not scar the scalp. It is reversible upon stopping the medication, and may stop with dose reduction [25].

Conclusion

Medication is vital to most people’s bipolar treatment plan. It is important to be aware of possible side effects and to bring them to your doctor’s attention as soon as possible, so that you can both decide on the best course of action for your health.
 
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If you think this article might help someone else too, please like and share.

All content within this article is for informational purposes only and is not intended to serve as a substitute for individual consultation with a qualified physician.

References

1. Fink, C. and Kraynak, J., 2016. Bipolar Disorder for Dummies. 3rd ed. New Jersey,                   USA: John Wiley & Sons, Inc.

2. WebMD. 2018. Lithium for Bipolar Disorder. [ONLINE] Available at: https://www.webmd.com/bipolar-disorder/guide/bipolar-disorder-lithium#2. [Accessed 22 March 2020].

3. UpToDate. 2019. Bipolar disorder in adults and lithium: Pharmacology, administration, and management of side effects. [ONLINE] Available at: https://www.uptodate.com/contents/bipolar-disorder-in-adults-and-lithium-pharmacology-administration-and-management-of-side-effects?search=lithium&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#H182696807. [Accessed 22 March 2020].

4. UpToDate. 2018. Lithium poisoning. [ONLINE] Available at: https://www.uptodate.com/contents/lithium-poisoning?search=lithium&topicRef=15317&source=see_link#H5. [Accessed 22 March 2020].

5. UpToDate. 2019. Unipolar depression in adults: Treatment with lithium. [ONLINE] Available at: https://www.uptodate.com/contents/unipolar-depression-in-adults-treatment-with-lithium?search=lithium&source=search_result&selectedTitle=4~148&usage_type=default&display_rank=3#H2519581674. [Accessed 22 March 2020].

6. UpToDate. 2020. Antiseizure drugs: Mechanism of action, pharmacology, and adverse effects. [ONLINE] Available at: https://www.uptodate.com/contents/antiseizure-drugs-mechanism-of-action-pharmacology-and-adverse-effects?search=valproate&source=search_result&selectedTitle=3~148&usage_type=default&display_rank=2#H1398705747. [Accessed 22 March 2020].

7. Mayo Clinic. 2018. Stevens-Johnson syndrome. [ONLINE] Available at: https://www.mayoclinic.org/diseases-conditions/stevens-johnson-syndrome/symptoms-causes/syc-20355936. [Accessed 22 March 2020].

8. UpToDate. 2020. Second-generation antipsychotic medications: Pharmacology, administration, and side effects. [ONLINE] Available at: https://www.uptodate.com/contents/second-generation-antipsychotic-medications-pharmacology-administration-and-side-effects?search=antipsychotic&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#H466014692. [Accessed 22 March 2020].

9. National Center for Biotechnology Information. 2012. First-Generation Versus Second-Generation Antipsychotics in Adults: Comparative Effectiveness [Internet].. [ONLINE] Available at: https://www.ncbi.nlm.nih.gov/books/NBK107237/. [Accessed 22 March 2020].

10. UpToDate. 2020. Second-generation antipsychotic medications: Pharmacology, administration, and side effects. [ONLINE] Available at: https://www.uptodate.com/contents/second-generation-antipsychotic-medications-pharmacology-administration-and-side-effects?search=extrapyramidal%20side%20effects&source=search_result&selectedTitle=3~150&usage_type=default&display_rank=3#H191681745. [Accessed 22 March 2020].

11. National Prescribing Service Limited. 2011. Antipsychotic monitoring tool. [ONLINE] Available at: https://resources.amh.net.au/public/antipsychotic-monitoring-tool.pdf. [Accessed 22 March 2020].

12. Hu, X., 2004. Incidence and duration of side effects and those rated as bothersome with selective serotonin reuptake inhibitor treatment for depression: patient report versus physician estimate.. Journal of Clinical Psychiatry, [Online]. 65(7), 959-65. Available at: https://www.ncbi.nlm.nih.gov/pubmed?term=15291685 [Accessed 22 March 2020].

13. UpToDate. 2020. Serotonin-norepinephrine reuptake inhibitors (SNRIs): Pharmacology, administration, and side effects. [ONLINE] Available at: https://www.uptodate.com/contents/serotonin-norepinephrine-reuptake-inhibitors-snris-pharmacology-administration-and-side-effects?search=venlafaxine§ionRank=1&usage_type=default&anchor=H276509267&source=machineLearning&selectedTitle=2~148&display_rank=1#H18324389. [Accessed 22 March 2020].

14. UpToDate. 2020. Serotonin-norepinephrine reuptake inhibitors (SNRIs): Pharmacology, administration, and side effects. [ONLINE] Available at: https://www.uptodate.com/contents/serotonin-norepinephrine-reuptake-inhibitors-snris-pharmacology-administration-and-side-effects?search=duloxetine§ionRank=1&usage_type=default&anchor=H1409194297&source=machineLearning&selectedTitle=3~99&display_rank=2#H1409194297. [Accessed 22 March 2020].

15. myDr.com.au. 2018. Tricyclic antidepressants. [ONLINE] Available at: https://www.mydr.com.au/mental-health/tricyclic-antidepressants. [Accessed 22 March 2020].

16. myDr.com.au. 2018. Monoamine oxidase inhibitors (MAOIs) for depression. [ONLINE] Available at: https://www.mydr.com.au/mental-health/monoamine-oxidase-inhibitors-maois-for-depression. [Accessed 22 March 2020].

17. benzo.org.uk. 2002. Benzodiazepines: how they work and how to withdraw. [ONLINE] Available at: https://www.benzo.org.uk/manual/bzcha00.htm. [Accessed 22 March 2020].

18. Patient. 2017. Benzodiazepines and Z Drugs. [ONLINE] Available at: https://patient.info/mental-health/insomnia-poor-sleep/benzodiazepines-and-z-drugs. [Accessed 22 March 2020].

19. WebMD. 2019. Benzodiazepine Abuse. [ONLINE] Available at: https://www.webmd.com/mental-health/addiction/benzodiazepine-abuse#2. [Accessed 22 March 2020].

20. Dols, A., 2013. The prevalence and management of side effects of lithium and anticonvulsants as mood stabilizers in bipolar disorder from a clinical perspective: a review.. International Clinical Psychopharmacology, [Online]. 28(6), 287-96. Available at: https://www.ncbi.nlm.nih.gov/pubmed/23873292 [Accessed 22 March 2020].

21. Nelson, J., 2017. Mindful Eating: The Art of Presence While You Eat. Diabetes Spectrum, [Online]. 30(3), 171–174. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5556586/ [Accessed 22 March 2020].

22. Better Health Channel. 2012. Weight loss - a healthy approach. [ONLINE] Available at: https://www.betterhealth.vic.gov.au/health/healthyliving/weight-loss-a-healthy-approach. [Accessed 22 March 2020].

23. NHS. 2019. Start losing weight. [ONLINE] Available at: https://www.nhs.uk/live-well/healthy-weight/start-losing-weight/. [Accessed 22 March 2020].

24. La Torre, A., 2013. Sexual dysfunction related to psychotropic drugs: a critical review part II: antipsychotics.. Pharmacopsychiatry, [Online]. 46(6), 201-8. Available at: https://www.ncbi.nlm.nih.gov/pubmed?term=23737244 [Accessed 22 March 2020].
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25. Kakunje, A., 2018. Valproate: It's [sic] Effects on Hair. International Journal of Trichology, [Online]. 10(4), 150–153. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6192236/ [Accessed 22 March 2020].

@BipolarLifeVic ​@finkshrink @WebMD  @UpToDate @MayoClinic @NPSMedicineWise @mydrwebsite
@patient @BetterHealthGov @NHSuk

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