CNS side effects: Mood changes, anxiety, dizzyness, sleep disturbance

About CNS side effects
Severe side effects
Reducing CNS side effects
How to report symptoms

Associated drugs: efavirenz (Sustiva), Atripla (contains efavirenz).

The side effects associated with efavirenz affecting the central nervous system (CNS) are not broadly linked with other anti-HIV drugs.

Although case reports of similar side effects have been reported with atazanavir/r, nevirapine, abacavir and other ARVs, these are very rare.

There are several difficult things about these side effects.

Firstly, nearly everyone will get some of these side effects but for most people they will be mild and easy to manage.

This means that you may have some strange dreams, or find yourself daydreaming or getting more worried, or you may get more upset than usual.

About a quarter of people in the first efavirenz studies recorded serious CNS side effects, including ‘difficulty carrying out daily work’.

Secondly, if you have been told about this before you start treatment, they will be easier to manage and should be less alarming. Information about what to expect before you start taking efavirenz is therefore essential.

Efavirenz CNS side effects can occur after a few hours or after several days and are more common over the first few weeks and months of treatment. They also generally reduce and become easier to tolerate.

About a quarter of people in the first efavirenz studies recorded serious CNS side effects. This definition included ‘difficulty carrying out daily work’. So although very few people stopped efavirenz in these studies because of the side effects, you have about a 25% chance that it could make it difficult to work as normal until you get used to them.

You should therefore start efavirenz at the weekend or when you have some time off work, when you are more relaxed and less worried or stressed.

Efavirenz may be a difficult drug if you work shifts that require sometimes working days and sometimes working nights.

Many of the symptoms described here can also be symptoms of HIV-related diseases that are now seen less frequently such as dementia, TB or cryptococcal meningitis. These can develop slowly over time, so describing symptoms to your doctor, in order that they can rule out these factors is very important.

Severe side effects

Person with black cloud hovering overhead Some people will experience these side effects much more intensely. If this is the case, it is essential that you get more support as soon as you need it. Perhaps 2-3% people switch to a different treatment very quickly.

But, more people only chose to switch after trying efavirenz for several months. Up to 20% people may switch over the first year or so.

This is because although side effects usually get esier to tolerate, they may continue at a low level for longer than the first few months.

CNS side effects can lead to or exaggerate clinical depression, including suicidal feelings and clinical paranoia. It is very important therefore that you are aware that such moods swings can be related to efavirenz and that you are not ‘going mad’.

If you are feeling paranoid and worried about going outside, or have stopped seeing your friends as much, this may be related to efavirenz side effects.

Why these symptoms are associated with efavirenz is not understood. It is also not possible to predict who will experience more severe symptoms.

Some studies have cautioned against using efavirenz if you are already depressed or have a history of psychiatric illness, but people without such a history have also found symptoms difficult.

Several reports have been published of severe reactions in people with no previous psychiatric symptoms or illness.

Some studies have linked higher efavirenz levels to low body weight. Importantly, research in 2004 showed that race may be an important factor. Several studies showed that a higher percentage of African women metabolise efavirenz more slowly. This results in higher doses than they need.

Often side effects are related to high blood levels of efavirenz. Measuring drug levels with TDM can allow dose reductions without reducing the HIV effect of the combination or risking resistance.

Several studies showed that some poeple, particularly African women, clear efavirenz more slowly from their bodies. This results in higher doses than they need.

Symptoms include:

impaired concentration, confusion and abnormal thinking.
mood swings including anxiety, agitation, depression, paranoia (feeling very anxious or nervous) and euphoria (feeling very happy).
sleep disturbance including insomnia, drowsiness, vivid dreaming and nightmares.

Measuring efavirenz levels with therapeutic drug monitoring (TDM) can allow dose reductions without reducing the HIV effect of the combination or risking resistance.

Reducing CNS side effects

Although you can take efavirenz with or without food, a high fat meal can increase drug levels by 60% and this can increase side effects.

Taking efavirenz a couple of hours before you go to sleep, rather than at bedtime, makes it more likely that you will be asleep when the drug levels are at their highest – about four hours after taking efavirenz.

Haloperidol to reduce anxiety and sleeping pills to help with sleep disturbance may also help, although these have not been formally studied.

If you have difficult side effects with efavirenz and you are not happy with how you feel, then change it for another NNRTI (nevirapine) or to a protease inhibitor.

Even if you have only used efavirenz for a few days, if you know it is not for you, you should change to a different drug. Many people use efavirenz without problems but some drugs are not for everyone.

You do not have to continue with efavirenz to prove anything to yourself or your doctor. If you know something is wrong, don’t worry about asking to change to something else.

Even if you have only used efavirenz for a few days, if you know it is not for you, it is okay to change. Some drugs are not for everyone.

How to report symptoms

Some of the symptoms associated with efavirenz are easier to decribe than others. The advantage of writing down the effects you experience will let you see whether they are getting easier.

Sleep disturbance

Keep a diary of how often your sleep is disrupted.
Try to describe this in a clear way. Is this every night or several nights a week?
Can you estimate how much time you sleep each night, and how much you slept in a normal night before you started treatment?

Other HIV drugs have also been linked to insomnia, though more rarely.

Concentration and memory

Are you finding it more difficult to concentrate?
Have you been aware of memory loss recently?

Dreams and nightmares

How often do you have dreams or nightmares?
Do these disturb you sufficiently to leave you unsettled the next day?

Mood changes

If you get mood changes try to describe these clearly in a diary.
Have our family or friends noticed a change in your behaviour, even if this is not clear to you?
Examples of how your mood has changed can give a clearer idea of how you are affected.

Depression and feelings of suicide

A small percentage of people who experience severe side effects have reported feelings of unexplained depression that are out of character, including suicidal thoughts.
Symptoms at this level mean that it is critical to discuss this with your doctor in order to change to another treatment.
If you are currently taking efavirenz, you may find it easier to talk to a close friend about how you feel and ask them to come with you for support when you visit your doctor. There is never a problem with taking a friend or family member with you whenever you see your doctor.