Side Effects of Antidepressants
As with almost any other pills, antidepressants has their own side effects.
For the first 2 weeks of taking an antidepressant, there may be little other than side effects. Generally, these will be mild. In some cases, however, they may be irritating or even intolerable. The first point to be made is that an antidepressant should only cause tolerable side effects. If treatment makes someone clearly worse, it should be stopped until advice has been sought and until that advice addresses the problem in hand.
Where side effects are more tolerable, there can be a great problem in distinguishing the effects of treatment from some of the symptoms of the illness. Both drugs and illness may cause a dry mouth, headache, indigestion, increased anxiety, sleeplessness or sedation for example.
There is a further unusual aspect to antidepressant side effects. When individuals are depressed, they are often much less sensitive to the effects of anything. They can’t smell, taste or hear as acutely before, for example. It is also common to find that sleeping pills don’t help the insomnia that goes with depression – even three to four times the recommended dose may not bring about sleep. After recovery, some people may be knocked by a low dose of the same sleeping pill that appeared inactive several weeks previously.
However, while some people are less sensitive to side effects when they are depressed, others seem more sensitive. It is very difficult, therefore, to predict the side effects that an antidepressant will have.
The side effects listed are typical. Some occur in everyone to some extent, depending on the particular compound, but they are usually mild and wear off after a few days. Even if they are severe, it should be noted that these side effects are reversible and will halt almost immediately on stopping the drugs.
As with the neuroleptics, there are two sorts of side effects to note. There are those which may feel like a worsening of the illness, like feeling more nervous, feeling strange or unreal, or even hearing voices. These latter side effects are the ones that need careful judgement.
Contents
- The obvious side effects of antidepressants
- The Ambiguous Side Effects of Antidepressants
- Antidepressants and suicide
- The Serotonin syndrome
- Antidepressants and mania
- Effects special to the MAOIs
- Special Conditions
- References
- Antidepressant Addiction Treatment
- Do You Need Help on Antidepressant Addiction?
The obvious side effects of antidepressants
Sedation
The tricyclic antidepressants and mianserin tend to be sedative when first taken. This sedation is quite like the effect of some of the older antihistamines (travel sickness pills). Just as with the antihistamines, about one-third of the people who have the tricyclic antidepressants are clearly sedated, while two-thirds will be either slightly sedated or not at all. Sedative effects may be quite unpleasant to begin with but they usually wear off in the course of a few days. In a minority of people, the sedation may persist, in which case the drug should be stopped, particularly if driving or work are compromised.
Some of the tricyclics, such as trimipramine and amitriptyline, are more likely to cause sedation than others. But sedation is as much a question of how sensitive one is to this particular drug as it is of the drug taken. Thus one individual may be heavily sedated by an antidepressant, while the same antidepressant may leave most other takers relatively unaffected or even aroused.
Arousal
Paradoxically the very same antidepressants that heavily sedate some people may cause others to be aroused. Usually, all tricyclics and mianserin are given to people at night time, as it is thought that their initial sedative effects will tend to help sleep. This can be particularly helpful in depression, as the disorder usually causes insomnia. However, rather than cause sedation, in about 1 person in 10, tricyclics may bring about an alerting effect, which can make sleep impossible. In this case, it makes more sense to take the pill first thing in the morning rather than last thing at night.
The MAOI antidepressants and mocobemide are more likely than the tricyclics to cause arousal. For this reason they are often given first thing in the morning rather than last night at night. However, while MAOIs are usually not sedating, in some cases they can be heavily sedating and have to be given last thing at night.
The SSRIs in most individuals usually have minimal effects on arousal or sedation. A proportion of people, however, are somewhat stimulated by them, while others are clearly sedated. Even more unusually, the 5-HT reuptake inhibitors appear sometimes to cause a subjective drowsiness while at the same time bringing about what is normally seen as a more ‘alert’ performance on tests of cognitive function.
Dry Mouth
An almost universal side effect of tricyclics, MAOIs, mianserin, lithium and the SSRIs is that they cause a dry mouth. This will usually be mild and, after the initial effects wear off, may be unnoticeable unless the taker has to talk at length – when there is a tendency for the mouth to become dry anyway. Occasionally, it may be severe to the point of feeling that the tongue is stuck to the roof of the mouth, or that the inside of the mouth feels like sandpaper. The nose may also be affected so that it feels dry and congested. In some cases of rhinitis (running nose), this may be seen as a helpful development.
For the most part, a dry mouth is a relatively minor inconvenience that may interfere with prolonged speech but little else. It can, however, be a more serious problem for some individuals, who may find the lack of saliva (which protects against tooth decay) can lead to an aggravation of dental caries.
It has been traditional to put dry mouths down to the anticholinergic properties of antidepressants. However, things may be somewhat more complex. Some of the more recently developed antidepressants, such as the SSRIs, which have been supposed to have little or no anticholinergic effects, also produce a dry mouth. Moclobemide is possibly the compound least likely to produce this side effect.
Fainting
Another prominent effect of tricyclics and MAOIs is that they tend to lower blood pressure. This shows up most clearly in situations when one stands up abruptly, such as getting out of bed, or standing up from a chair in which one had been sitting for some time. For most of us abrupt changes in posture like this can produce a feeling of faintness or a slight hint of seeing stars. This may become marginally more exaggerated or it may become very marked, so that minor changes of posture may cause a subject to topple over. This can lead to quite serious falls and injuries. This is a particular hazard in older individuals for whom changes in posture are even more likely to cause drops in blood pressure.
Palpitations
Palpitations are one of the more unsettling effects of an antidepressant. The experience of having one’s heart beating irregularly or thumping in one’s chest is alarming although, in fact, palpitations are usually harmless. The commonest cause comes from the heart trying to compensate for a drop in blood pressure by potting out more blood pressure by putting out more blood. There may be a real hazard, however, for individuals who have had heart trouble before starting antidepressants; and these individuals should be assessed with greater care.
Urinary difficulties
All antidepressants, but tricyclics and MAOIs in particular can cause trouble in passing urine. In the mildest cases, people will be marginally aware that there is a slight delay before micturition. There may also be a feeling of distension around the bladder area, which causes a feeling of fullness just above the pubic bone. This may be uncomfortable and even painful. Textbooks usually list these symptoms as affecting men only but they also affect women. Occasionally the problem may be more marked to the point of having clear difficulties in micturition, even to the extent of having to be characterised for urinary retention. This latter is most common in older men with enlarged prostate glands.
While this side effect is usually put down to the anticholinergic properties of tricyclic antidepressants, there also appears to be a 5-HT input to the bladder, so that SSRIs may produce something of an increase in bladder capacity, with drugs that block 5-HT-2 receptors (e.g. clozapine) producing a decrease.
Sweating
It is not common for antidepressants, especially tricyclics, to produce sweating. This is particularly common in hot weather. It may be most noticeable at night when it can lead to waking to find the sheets drenched. Increased perspiration may also be a feature of the serotonin syndrome.
Shake / Tremor
In some cases, individuals on an antidepressant may find they have a shake of their hand or arm. This is commonest on high doses. If it happens it may mean that the dose is too high. In some individuals, because of differences in rates of absorption the usual clinical dose may be too high and may need lowering. A shake is one hint that this may be the case.
Twitch / Jerk
It seems that all antidepressants are likely to cause twitches or jerky movements (myoclonus) of the head, arms or legs. These seem to be commoner in the legs at night but may affect any part of the body at any time. This is a side effect of antidepressants rarely noted in any books but, surprisingly, it appears to happen to a significant extent in up to 10% of takers. It may be commoner with drugs active on 5-HT system. It usually stops on switching to another treatment.
Teeth Grinding (Bruxism)
A further, rarely described side effect is teeth grinding. This is something many of us do during sleep anyway, but in some cases, and again possibly more commonly with the SSRIs, teeth grinding can begin during the day. It may get so intense as to cause marked gum pain. Those who can remove dentures do so, but at the cost of embarrassment. Occasionally the problem may be sufficiently severe to lead a grinding down of the teeth. There may be two distinct components to the problem: abnormal movement of the jaw (a dyskinesia) and an increase in tone of the jaw muscles, which may be painful in its own right. Both problems appear to resolve with a change of treatment.
Headache
Headaches are a common feature of depression, and therefore it is difficult sometimes to be sure if an antidepressant has caused them. The kind of headache caused by medication is usually slightly different to that found in depression itself. Typically, it is muzziness or feeling of painful fullness, rather than the aching tension type of headache that all of us have had at some point or other. It may not be possible to distinguish these headaches, however, and therefore if a new headache comes on after starting an antidepressant, or the old one seems to get worse, it may be wise to seek advice.
In rare instances, antidepressants may trigger migrainous headaches, that have a throbbing, pulsating character and which usually affects one side or other of the head, and may be accompanied by disturbances of vision and/or nausea and vomiting. The reason for this appears to be that most of these drugs act on 5-HT system, which is probably involved in migraine. Whether the ordinary kind of headache or a migraine, headaches will almost certainly be harmless. The issue is whether they are too uncomfortable to put up with, rather than whether they are serious.
In a small proportion of cases they may, however, be serious. This applies particularly to individuals who are on MAOIs and who have eaten food containing tyramine. It may also apply to individuals who are taking lithium. Headaches are also likely to be more serious when they occur in someone taking combinations of treatments, such as antidepressants and neuroleptics, antidepressants with lithium, or lithium with neuroleptics.
Blurred vision
A further side effect of most antidepressants is blurred vision. This is particularly likely to happen with some of the older drugs, which have the most marked anticholinergic effects. While this is listed as one of the obvious side effects of antidepressants, it is surprising how often it leads people to make appointments to get their eyes checked. It is important not to have an eye appointment for failing eyesight and a possible change of glasses until after the drug has been discontinued at which point, if there is still a problem, advice should be sought.
Occasionally, individuals probe to glaucoma will have their condition exacerbated and it will be necessary to prescribe an antidepressant with minimal or no anticholinergic effects. For those who do not know they are prone to glaucoma, the condition if it is aggravated presents with acutely painful eyes. It must be stressed, however, that this is a very rare occurrence.
Weight Gain
Depression commonly leads to a loss of appetite, and a loss of weight. Treatment with antidepressants, therefore, can be expected, by restoring appetite, to lead to some weight gain in all of us. For some individuals, however, there is a far more serious weight gain than this. They may put on up to 10-15 kg, for reasons that are not fully understood. Weight gain may be aggravated in individuals who are also taking lithium and neuroleptics.
Until recently there was no option as regards the issue of weight gain because all of the antidepressants in use were liable to cause the problem. The SSRIs, however, do provide an option now. These drugs, in general, have an appetite suppressing property. In some cases they may cause nausea and even vomiting. The nausea generally subsidies within a few days but a mild suppression of appetite can remain.
While weight gain may seem like an obvious side effect of drug treatment, many individuals seem unaware that their drugs can be causing them to gain weight, and accordingly they may try to diet strenuously, abetted by their general practitioner. Their inability to lose weight in the expected way may be quite demoralising.
Nausea
All antidepressants may cause nausea. They may also cause indigestion, constipation and a bloated feeling. The SSRIs, however, are far more likely to cause nausea and indigestion than any of the others. Up to 30% of people who take these drugs may feel nauseated, as though they were sea-sick. This usually wears off after a few days. In some cases, however, it may be quite severe, may lead to vomiting and may not wear off. In such cases the drugs have to be stopped.
The addition of lithium to another antidepressant is particularly liable to lead nausea. It seems that nausea in all these instances is brought about by a sensation of 5-HT receptors in the gut.
The ambiguous side effects of antidepressants
Dissociative reactions: Depersonalization, derealization and other reactions
Depersonalization refers to the experience of feeling strange and unusual, almost as though you are not really yourself anymore, or that you are operating in a kind of a dream or haze. It refers to the unreal feeling that many of us may have at interviews or other stressful situations where part of us seems to be functioning automatically and not under full control.
Derealization describes a similar set of feelings and perceptions as they apply to the world rather than to the self. It refers to a state in which the world seems strange or unreal; everything may seem far away or staged in some way, as though life is being watched rather than lived.
These feelings happen in anxiety states, but they also happen commonly in depression as well. If, however, they start for the first time after taking an antidepressant, or get clearly worse, treatment should be discontinued. The sensations will go within hours or, at the most, days after stopping treatment and are not serious although, like palpitations, they may be very unsettling experiences.
Their danger lies in the fact that they may be interpreted by the person taking the antidepressant, or others, as evidence that the illness is getting worse, or that some brain damage of some sort has been caused that may be permanent. While they are not in themselves serious, the reason for stopping the drug that has caused these reactions is that it is most unlikely that this drug would cure depression in an individual who is having marked dissociative reasons like these.
Other dissociative reactions have also been reported. These include:
- A feeling that time is standing still.
- Deja vu experiences.
- Prominent nightmares.
- Out-of-body experiences.
- Amnesia.
- Auditory or visual hallucinations.
In some cases of amnesia, an individuals on antidepressants may find his memory clearly impaired. Subsequently, on discontinuing the drug, he may find it difficult to remember what it is like to be on it, and a number of the things that happened to him whilst on treatment.
Hallucinations are more likely in elderly people but can happen to anyone. They are not serious and clear up once the drug is discontinued. The problem arises when the experience prompts people to think that their illness must be getting worse because ‘everyone knows voices are a sign of lunacy’.
Confusion / Disorientation
Rare but serious is the occurrence in some individuals, especially older people, of quite marked confusion. This is probably quite closely related to depersonalisation. In the case of depersonalisation, individuals ordinarily know that things are not quite right, yet are able to operate normally and appear to outsiders to be quite normal. The confusional reactions go one step further in that it becomes quite obvious to all concerned that something is not quite right. An affected subject may get to the stage of being quite disorientated and as a consequence quite agitated. This may lead to their being over-active in a way that potentially puts them at risk to themselves or to others.
Added to this is the fact in rare instances, again especially in the elderly, tricyclic antidepressants and MAOIs can cause hallucinations. Combined with a confusional reaction, the occurrence of hallucinations can produce a picture of what looks like an almost full blown insanity. The fact that it all clears up quickly once the drugs are stopped indicates that what is involved is a side effect of treatment rather than any change in the individual’s mental balance.
The dissociative reactions to antidepressants are relatively rare. They may however be of tragic significance if misinterpreted.
Sexual Side Effects
The issue of sexual side effects of psychotropic medication will be dealt with more fully at a later stage. As with the neuroleptics, there is a general coyness about enquiring about the effects of antidepressants on sexual functioning and hence the information is limited.
In men, antidepressants may cause difficulty in sustaining an erection or in ejaculation, but exactly how often is uncertain. Estimates have been building recently, with suggestions that up to 50% of those on tricyclics and more than 80% of those on SSRIs have notable effects. The distress that this causes is also unclear but presumably it will lead some people to discontinue treatment. There are cases, however, where delayed ejaculation can be helpful, and there is growing use of SSRIs for this purpose.
There is further unusual effect on ejaculation which is retrograde ejaculation. In this case, owing to altered sphincter tone, the seminal fluid passes backwards into the bladder on ejaculation rather than forward in the usual manner. This effect may only be noticed later when the affected person notices that their urine is cloudier than usual.
The antidepressant for which all these effects are most clearly documented is clomipramine, which can cause difficulties in up to 80% of men taking it. For the most part, however, when this is being taken to ameliorate obsessional symptoms, most takers appear happy with the trade-off between an easing of their symptoms and sexual impairments. On withdrawal, clomipramine may produce the opposite-repeated unwelcome orgasms, in both men and women. Clomipramine appears to produce these effects mainly through an action on 5-HT reuptake. Nor surprisingly, therefore, the SSRIs produce similar effects, which can range from an inhibition of erection and/or ejaculation to just the opposite.
The opposite side effects most likely to happen is priapism – that is sustained erection of the penis. If mild, this may be welcome development but in some cases, the erection produced may be so full as to be painful or may be so sustained – 12 to 24 hours – that it causes permanent damage to the tissues of the penis. In such cases, surgical relief may be required. The antidepressant most likely to cause this is trazodone, and the effect is thought to be mediated through both noradrenergic and 5-HT receptors.
Effects on erectile functioning are the most obvious of the effects on the sexual system. What is much less clear is the effect of antidepressants on interest in sex (libido). A reduction in libido is a common feature of depression, and reduced libido often seems to be one of the last things to return to normal, when a depression clears up. Over and above this, however, there is some evidence that antidepressants may in a minority of cases actually reduce libido further, although compounds which act on 5-HT-2 receptors such as trazodone and nefazodone may do the opposite and enhance libido.
The effects of antidepressants on sexual functioning in women are somewhat more clear than the effects of neuroleptics. The SSRIs and clomipramine are liable to cause a failure of orgasm in women in exactly the same way as they inhibit ejaculation in men. Women may complain about this less than men but there is no reason to believe that it occurs any less frequently in women than men.
As with men, trazodone and nefazodone are likely to lead to an increase in libido. The effects of other antidepressants on libido are less clear in that libido is commonly lost in the course of a depressive disorder and restored when the disorder clears up; whether a particular compound delays the recovery of libido or not has been very difficult to gauge against the background of depression.
Other possible changes involve disturbances to the frequency or intensity of periods or both, and changes in breast size, tenderness or both.
The reason for including the sexual side effects of antidepressants in this section is because any impairments of sexual functioning are all too liable to be interpreted by depressed individuals as personal failings – further evidence of their inadequacy. All sexual side effects appear to be reversible on discontinuation of the drugs.
Of the currently available compounds, moclebemide appears to be the most neutral in its effects on sexual functioning – neither inhibiting nor enhancing sexual functioning. (Increasing libido in a subject who is not expecting it may cause problems).
Restlessness / Akathisia – Agitation
This side effect, common with neuroleptics, was thought to be uncommon with antidepressants, but is being increasingly recognised and increasingly thought to be significant (see suicide below). It may occur within hours of starting an antidepressant or take up to 2 weeks to appear.
The feeling is one of twitchiness and inability to keep still, a feeling of nervous discomfort, as though one’s nerves had somehow become ‘live’. Such effects can be quite uncomfortable and, perhaps not reasonably, may lead some people to abandon their drugs.
This kind of restlessness seems to be most liable to happen in the case of subjects who are anxious or agitated to begin with. It is particularly marked when antidepressants are given to patients who have panic disorder. Such patients may be made much worse if put immediately on a high dose, such as 75 mg at night of a tricyclic antidepressant, increasing after a day or two to 150 mg. In the case of highly anxious patients it seems better to start a lower dose and to work slowly up to a higher dose.
A more classic neuroleptic-like akathisia also appears to happen and appears at present to be more common with the SSRIs. The drug for which this has been most clearly described is fluoxetine, but it seems likely that it applies to most tricyclics and other SSRIs also.
There is a further state, which is probably related to both of these which may be better described as tension or agitation rather than restless. In this case an affected individual will not be obviously jittery, or restlessly move his legs or body, but will feel increasingly tense.
Antidepressants and Suicide
Depression brings with it a risk of suicide. There is no generally accepted theory of why depressed individuals commit suicide. It has been widely noted that one of the times people are most likely to attempt to kill themselves has been around 10-14 days after starting antidepressant treatment. The rationale sometimes given for this is that depression causes both a slowing up (psychomotor retardation) of the affected individual and suicidal ideation. Antidepressants are then supposed to clear up the retardation before they have effects on suicidal thoughts. This it is argued leads to individuals having the necessary drive and the energy to effect their own demise, in a way that was not possible when they were extremely slowed up in themselves.
While this may be true in some cases, research suggests that this is not the only reason why individuals may commit suicide while on antidepressants. It now seems likely that the occurrence of restlessness, tension, or dissociative reactions while on antidepressants may lead to suicide attempts.
There is some dispute as to why this should be the case. My personal opinion is that subjects on antidepressants who find themselves feeling depersonalised or restless sometimes reason that what is happening is that their nerves are getting worse. As this happens despite their being on treatment, they conclude that they are incurable and there is no option other than suicide. This is particularly likely to be the case in instances where the restlessness is quite intense, as it may be. This rationale may even apply if the subject believes the drugs to be responsible for her feeling worse and discontinues treatment – only to find no immediate relief. In this case, an individual may conclude (incorrectly) that the drug has done permanent damage to her nervous system. An increasing number of cases of this sort are being recognised. Impairments of sexual functioning of one sort or another are a further side effect that could conceivably produce a similar outcome.
The SSRIs, and newer agents such as moclobemide, are clearly safer in overdose than the older tricyclic compounds, and this initially led to hopes that their use might be associated with a lower incidence of successful suicide. However, a number of recent studies cast doubt on this, in particular a large study by Jicks and colleagues, tracking the outcomes of 172,000 subjects treated by their GPs found a higher rate of successful suicides (by any method) in subjects taking newer as opposed to older antidepressants that could not be explained by supposing that the more severely depressed patients had been given the newer drugs.
The Serotonin Syndrome
Antidepressants, and in particular the SSRIs, may produce a picture, which has similarities to the neuroleptic malignant syndrome will be described in Side Effects of Neuroleptics. A group of side effects, which may all have in common an excess of 5-HT, may occur in this condition. The occurrence of any one of these side effects on its own is not a cause for alarm, it is their conjunction that constitutes the serotonin syndrome and which, although not as serious as the neuroleptic malignant syndrome, does need urgent attention.
The commonest feature of the syndrome is myoclonus (jerks and twitches). This occurs up to 40%. Tremors of the tongue or fingers occur in 25%, as does shivering and sweating. Up to 20% of subjects may be confused, agitated or restless. In 15% there may be evidence of hyper-reflexia and in 10% diarrhoea. Little is known of the subjective nature of the state, at present.
At least three of these symptoms should be present before making a diagnosis. Even then, the condition may simply respond to halting treatment. It is not clear how often the condition actually occurs and simply clears up without anything specific being done. However, this condition may also be more serious, requiring hospitalisation and the kind of support available intensive care units. A small number of fatalities have been suspected.
As the name implies, it is thought that the disorder stems from an excess of serotonin. It probably first began to occur when individuals were put on combination of MAOIs and tricyclic antidepressants, especially those such as clomipramine which inhibit 5-HT reuptake. It appears to have become more common with the recent availability of more potent SSRIs. Combining these with other drugs that act on the 5-HT system, and / or MAOIs, appears liable to trigger the state.
The combination of MAOIs and tricyclics or SSRIs is generally reserved for depressive conditions that are relatively resistant to monotherapy. Where undertaken, there are some indications that moclobemide may be a safer bet than the older MAOIs and citalopram or paroxetine safer than other SSRIs or tricyclics on the basis that they affect fewer neurotransmitter systems.
Antidepressants and Mania
Intuitively it would seem that drugs which elevate mood could go too far and precipitate someone into a manic state. However, ECT and lithium are both antidepressants and at the same time are antimanic. Yet some people on antidepressants become elated. Why?
This issue will be treated in more detail in the articles on mania and on lithium. Briefly it seems that individuals who are liable to both depression and mania rather than to depression alone have always been liable to mania when swinging out of a depression, whether treated with antidepressants or not. The opposite is also true. When on their way down, people who have been elated, often overshoot and have episodes of depression. These, for the most part, are brief. Similarly, for the most part, the episodes of mania on swinging out of depression, tend to be brief rather than full blown and lengthy. One possibility, therefore, is that antidepressants do not cause mania but by successfully bringing depressions to an end also bring forward potential episodes of mania.
What should be done if someone becomes elated while on an antidepressant? The generally accepted wisdom is that treatment with the antidepressant should be halted and treatment for mania possibly started – although the logic of the argument above would suggest that in some cases continuing with an antidepressant for a while may not be any harm. It is important, however, to distinguish between a manic episode proper and the hyperactivity that may stem from mild confusion or a stimulant effect from mild confusion or a stimulant effect from one of the other MAOIs in particular. Such reactions require treatment to be halted and should clear up quickly following discontinuation.
Effects Special to the MAOIs
The Cheese Effect
A particular hazard of the older MAOIs is the cheese effect. This is so called because it was noticed first following reactions to cheese in people taking MAOIs. What happened was that the blood pressure of subjects who were on MAOIs, who ate certain kinds of cheeses, went up dangerously high. This was first noticed in some subjects who developed headaches, neck stiffness and began to perspire flush or vomit. As this increased blood pressure could potentially cause a stroke, there was concern. Indeed some fatalities on MAOIs have been put down to just such a mechanism, although there is some dispute about this.
What appears to happen is that cheese contains a substance called tyramine which leads to increases in blood pressure. This is normally broken down in the gut, by MAO, so that it doesn’t get into the body. The MAOIs prevent this breakdown and hence tyramine enters, cannot be metabolised in the body and leads to an increase in blood pressure.
This means tyramine containing foods should be avoided. All cheeses except cottage, Danish brie, Danish camembert and cream cheese contain significant amounts of tyramine. This means avoiding pizzas, which have mozzarella cheese as an ingredient or pasta dishes with parmesan cheese on them.
Other foods containing tyramine include:
- Avocado.
- Bananas.
- Caviar.
- Canned figs.
- Pickled herrings.
- Liver.
- Smoked or fermented sausages – including pepperoni and salami.
- Yeast extracts – including Bovril, Marmite and Oxo.
- Broad bean pods, which are sometimes eaten when beans are young.
Wines and beers contain modest amounts of tyramine. This is particularly the case for Chianti wines and most beers or ales. In general it is advised that only fresh food should be eaten. If there is any hint that food, such as meat, eggs or poultry may be going off it should be avoided – game, for example, cannot be eaten.
For the most part, except for some cheeses, pickled herrings, caviar sausages and Marmite, the amounts of tyramine in the other foods listed above are unlikely to cause significant problems. But, on the principle that it is better to be safe than sorry, all the above are usually held to be unsafe. However, the combined effect of avoiding all the foods listed above is a considerable interference with normal living and for this reason the MAOIs are not usually used as the antidepressant of first choice, tending now to be used most commonly in individuals who neither tolerate the side effects, nor respond to tricyclics.
While all the above foods may cause trouble, they do not usually do so. There is no need for anyone to rush to hospital if they are on an MAOI and have suddenly realised that they have just been having cheese and wine. Unless there is a clear feeling of illness, such as the onset of a headache or temperature, or a stiffness of the neck, the odds are that there will be no harmful effect.
Moclobemide appears relatively free of the cheese effect. Large amounts of tyramine will displace the drug from the enzyme which means that above a certain level the tyramine is metabolised. As a result even cheese and wine in normal quantities can be taken safely – it would take extraordinary quantities to cause a problem.
Special Conditions
Pregancy
At present there seems to be no good evidence that the older tricyclic or MAOI antidepressants cause a significantly increased risk of abnormalities in the foetus. There appears, therefore, to be no pressing need to discontinue treatment in someone who finds themselves pregnant if, otherwise, it seems a good idea to continue. If a pregnancy is being contemplated, however, or if there is no clear need to continue with treatment, it may be wiser to stop treatment. Rebound reactions have been noted in infants born to mothers taking antidepressants at the time of labour. These include restlessness, irritability and insomnia. They last for a few days.
The situation is somewhat different for lithium. It is also different for the SSRIs. There is much less experience with these compounds and hence the risks are less certain although to date no notable problems have been reported.
Both tricyclics and MAOIs enter breast milk in small amounts but appear to be of no risk to babies being breast fed.
Cardiac Conditions
A further complication of antidepressant treatment, which can now be avoided because there are a number of different classes of agent available, concerns the possible effects of these drugs on the heart. For all of us tricyclic and MAOI antidepressants can be shown to have demonstrable effects on the electrical conduction of our hearts. Such effects are not necessarily harmful, and, indeed, in a number of therapeutic situations where the heart is not working properly, in particular when it is beating irregularly, such effects can be helpful.
However, in individuals who have compromised cardiac function, who have recently had a heart attack, who have angina or disturbances of cardiac rhythmicity, the effects of these antidepressants are unpredictable. Therefore individuals who have any cardiac problems or who have reason to believe that they might have a cardiac problem, should have their heart investigated and the potential effects of an antidepressant on it determined before a course of treatment is started.
These problems can now be overcome by the choice of an alternative antidepressant. Many of the more recently developed antidepressants, such as the SSRIs or moclobemide, are largely free of cardiac effects and can be taken without concern.
There is one side effect of not here that does not amount to what it seems. A cardinal sign of cardiac failure is swelling of the ankles, as fluid is retained in the body. The MAOIs occasionally cause ankle swelling but not normally because there has been any cardiac failure.
Epilepsy
A further complication of tricyclics that has been overcome by the newer agents concerns their interaction with epileptic disorders. Due to their effects on electrical conductivity, the tricyclic and MAOI antidepressants alter electrical thresholds. The case of epilepsy this can actually be beneficial and make the occurrence of an epileptic fit less likely.
But there can be a problem when the drugs are halted. The changing electrical thresholds that occur at this point in time may trigger a seizure. As halting can be accidental, as for example forgetting to take the drugs one night, this issue can be a problem for subjects with epilepsy. Again the newer drugs such as the SSRIs seem to be relatively free of this complicating factor.
Other Conditions
In the case of liver, kidney, prostate problems or glaucoma caution should be exercised. Liver and kidney problems may require a lower dose of the drug as it otherwise tends to build up in the body. Glaucoma and prostatism require the choice of an antidepressant less likely to precipitate problems – one with less anticholinergic effects.
Overdoses
In general the antidepressants are very safe drugs. Despite the fearsome list of side-effects just covered, they rarely cause problems when handled properly. The exception is in the case of overdoses. By far the most important danger with antidepressants stems not from taking a tricyclic antidepressant in the presence of an unsuspected cardiac condition, or accidentally combining an MAOI with cheese or wine, but rather from overdosage. Antidepressants differ from most other drugs in psychiatric use in that they are liable to be fatal in overdose. This was particularly the case with older tricyclic and MAOI antidepressants. Overdoses of a relatively modest amount of these pills can kill. Death is by interference with cardiac conduction causing the heart to beat irregularly or stop, or is brought about by causing convulsions.
There is much less risk with the newer antidepressants. Consumption of very large amounts of mianserin, lofepramine or SSRIs (300-400 tablets in some cases) seems not to be fatal.
Driving
With the development of the less sedative SSRIs concern began to be noted about the possible behavioural toxicity of older antidepressants and in particular their possible role in causing road traffic accidents (RTA). The first point to note here is that untreated illness probably poses a far greater hazard in the main than do the effects of treatment, the second is that the risks associated with taking the older compounds have not yet been established, a third is that there can be considerable inter-individual variability in the effects of drugs on a performance such as driving and finally any such risks seem likely to be of much less practical importance than the risks posed by drinking and driving.
Having made these points, individuals who are on a cocktail of drugs, who are clearly sedated by their drugs and who have just started a drug regime should be advised not to drive or to assess responsibly whether their performance is or is likely to be affected. This particularly applies to the driver of heavy goods vehicles or those driving coaches or other passenger carrying vehicles. While the legal responsibility to issue such warnings may strictly lie with the medical prescriber, in practice those who may be best placed to judge the extent of any risks, apart from the patient, may be friends, relatives or key workers.
References
- Creaney W, Murray I, Healy D: Antidepressant induced suicidal ideation. Hum Psychopharmacol 1991, 6:329-332
- Healy D: The fluoxetine and suicide controversy. CNS Drugs, 1994, 1:000-000
- Jick SS, Dean AD, Jick H: Antidepressants and suicide. BMJ 1995, 310:215-218.
- Sternbach H: The Serotonin syndrome. Am J Psychiatry 1991, 148:705-713.
- Lejoyeux M, Ades J, Roullion F: Serotonin syndrome: incidence, symptoms and treatment. CNS Drugs 1994, 2:132-140.
- O’Hanlon JF: Minimising the risk of traffic accidents due to psychoactive drugs. Primary Care Psychiatry 1995, 1:77-85.
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