Managing acute manic episodes

Sleep deprivation, especially REM sleep deprivation, not only treats depression rapidly and effectively, but it may even induce mania. This provides the basis for the theory that insufficient sleep, again primarily insufficient REM sleep, is an important cause of mania.

Accordingly, to treat an acute manic episode, we need to increase the amount of REM sleep. The propensity for REM sleep is determined by our circadian rhythm, with the highest likelihood of having REM sleep during the hours following our usual wake time (if we happened to be asleep then). Therefore, to increase REM sleep, we need to address two components: first, establish a stable circadian rhythm, and second, within that stable circadian pattern, get sufficient sleep with the right timing.

A stable circadian rhythm is easiest to achieve by getting up at the same time every day, seven days a week, no exceptions. Pick an arising time that will be sustainable when well, ie that gets you up in good time for work or school.

Working backwards from this arising time, pick a bedtime that will provide about 7 hours of sleep (for most adults). Thus, for an arising time of 6 am, bedtime would be 11 pm in order to get 7 hours in bed.

Because acute mania usually involves sleeping very little, the second component, getting sufficient sleep with the right timing, requires:

1. Reducing or eliminating environmental factors and behaviours that interfere with sleep;
2. Implementing strategies that promote sleep;
3. Medication to increase sleep.

Let’s address each of these in turn.

Behaviours that interfere with sleep

• Exercise in the evening
• Stimulants (eg, caffeine) in late afternoon or evening.

Short, but intense, exercise in the morning helps to improve or maintain cardiovascular fitness. For example, five minutes on a rowing machine.

As with sleep, we do best if we have the same daily dose of caffeine, spread out over the morning and early afternoon. Coffee, even decaf, contains chlorogenic acid which lowers insulin levels, and therefore is useful against metabolic syndrome, type 2 diabetes, and possibly other conditions of aging such as cancer and dementia.

Environmental factors that interfere with sleep

Blue light, including from computer or mobile device screens, suppresses melatonin. Since the cyclical production of melatonin is an essential component of our circadian rhythm, we do not want to interfere with it.

1. Make sure the sleeping space is dark. Blackout curtains or blinds may be necessary;
2. Night lights (eg for the bathroom) should be red or pink, NOT blue, green, or white;
3. Eliminate sources of blue light. This includes the blue or white LEDs found on many electronics devices. Take the electric toothbrush off its charger, if it has a blue LED;
4. If using an electronic device in the evening, switch it to “night shift” mode (on Apple devices; “NIght Light” on Windows 10; “Night Mode” on Android) to reduce the amount of blue light from the screen. Also, reduce brightness!

Strategies to promote sleep

The usual recommendations for good sleep also apply. In no particular order:

• Quiet;
• Cool (turn down the thermostat a couple of degrees at bedtime);
• A comfortable mattress or pillow;
• For GERD (Gastro-Esophageal Reflux Disorder) sufferers, raising the head of the bed and sleeping on one’s left side may help. Ranitidine or famotidine are available over the counter or by prescription;
• Individuals with OSA (Obstructive Sleep Apnea) may benefit from CPAP or variants such as BiPAP;
• Avoid daytime naps. No morning naps at all. Afternoon naps, if short (15 or 20 minutes) may not interfere with nighttime sleep;
• If worry keeps you awake, write down a reminder of what you need to do to address the problem.

Medication to increase sleep

A number of psychotropic medications are quite sedating. This is typically considered an undesirable side effect, but for treating acute mania, it’s a side effect that can be used as the primary treatment. Clinical experience suggests that the medication methotrimeprazine (known as levomepromazine in some parts of the world; brand name Nozinan¹) is highly effective. Used many years ago as an antipsychotic, with an antipsychotic potency similar to chlorpromazine (Largactil) it has long been out of favour for this purpose, along with other low-potency drugs of the era. But because it is highly sedating, methotrimeprazine continues to be used, for example in palliative care. The doses used for sedation are often one or two orders of magnitude lower, and therefore much safer even in frail elderly, than the 400 to 800 mg per day that would have been used for a young adult with schizophrenia.

Methotrimeprazine or any other sedating medication used to increase sleep should be administered only once per day, prior to bedtime. This is to avoid daytime sedation, but even more importantly to reduce development of tolerance to the medication. Many people do well if an oral dose is given an hour before bedtime. If by injection, it typically acts rapidly, and so should be administered 15 to 30 minutes before bedtime.

Methotrimeprazine can be started with a single nighttime dose of 10 mg (5 mg in elderly). If the amount of sleep obtained is insufficient (that is, waking before the desired rising time and unable to return to sleep) increase the dose in small increments.

Another highly sedating medication is clonazepam (Rivotril). This benzodiazepine, like others in this class of medication, will induce tolerance. Once a significant degree of tolerance has built up, stopping the medication suddenly can induce serious withdrawal symptoms, including life-threatening status epilepticus. Fortunately, clonazepam has a long half-life, which reduces risk for serious withdrawal symptoms.

Other useful interventions

Maintaining a consistent daily schedule for other activities, such as meals, exercise, or other activities, will also help to stabilize circadian rhythm.

Avoid stimulating activities such as loud music, parties, sports events or concerts.

Melatonin is available over-the-counter as a supplement. A tablet combining 5 mg of rapid release with 5 mg of timed release melatonin may help individuals to fall asleep and stay asleep.

When individuals are agitated or combative due to their mania, antipsychotic medication can be helpful. However, these should be administered only as needed, and only ones that are nonsedating.

Manic episodes are often triggered when an individual decreases or stops taking mood stabilizing medication eg lithium or valproate. Such medication should be restarted, in gradually increasing doses if necessary, and with careful monitoring of blood levels and side effects.

Medications to be avoided

The mechanism of action of benzodiazepines involves the same receptors in the brain that are affected by alcohol, so problems from alcohol consumption including accidents, falling, aggressive behaviour, depression, and suicidal behaviour can also occur with benzodiazepine use. In contrast, methotrimeprazine (also known as levopromazine; trade name Nozinan), being an antipsychotic, may diminish aggressive or impulsive behaviour.

Short-acting benzodiazepines, much like alcohol, will induce sleep initially, but may produce a rebound insomnia later on in the same sleep period.

Antidepressant medications, sometimes prescribed for individuals with bipolar disorder, may induce a manic episode. But even short of full-blown mania, antidepressants may cause manic symptoms such as anger, irritability, or impulsivity even while the individual remains depressed. Antidepressants therefore should be tapered in people with mania or having symptoms associated with mania. Stopping an antidepressant suddenly or even decreasing too rapidly can bring about a “discontinuation syndrome” which can be extremely uncomfortable for the individual. Another risk of rapid decrease is a rapid slide into profound depression, including suicidality.

1. Note that in Canada, Nozinan under its tradename is available only in liquid form for injection. For tablets (available as 2, 5, 25, or 50 mg) it needs to be prescribed as methotrimeprazine maleate. ↩

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