For the first few weeks on an antidepressant, side effects rather than benefits often predominate. If the pill is ultimately going to be suitable for the person taking it, the side effects will generally be mild. Antidepressants should cause only tolerable side effects. If treatment makes someone clearly worse, it should be stopped until advice addresses the problem in hand.
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Side effects of antidepressants
There may, however, be great difficulty 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, anxiety, sleeplessness, feelings of unreality and even suicidality or aggression. The difficulties in discriminating what might be stemming from what are brought out beautifully in Rebekah Beddoe’s Dying for a Cure. 22
There are a number of other unusual aspects to the side effects of antidepressants. In severe depression, individuals are often much less sensitive to the effects of anything. They may not smell, taste or hear as acutely as before, for example. Even three to four times the dose of a sleeping pill may not help the insomnia that goes with depression. The same people, a few weeks later when they have recovered, may be knocked out by a low dose of the same sleeping pill. This, however, is much less likely to apply to patients with a milder form of depression or anxiety, who are now most likely to be prescribed antidepressants. Those who are anxious may be more rather than less sensitive to the side effects of antidepressants. It is difficult, therefore, to predict the side effects that an antidepressant will have.
In addition, there can be huge variation according to personality type and ethnic background, with certain personality types susceptible to certain side effects while others are not and some ethnic groups liable to difficulties that do not happen in others. Thus Japanese men seem prone to gynaecomastia on selective serotonin-reuptake inhibitors (SSRIs) whereas Caucasians are not.
The side effects listed on the next pages are the typical ones. Some of these occur in everyone to some extent, depending on the compound they are on, but they are usually mild and wear off after a few days. For the most part, these side effects are reversible on stopping the drugs.
As with the antipsychotics, there are two sorts of side effect to note: those that seem more like side effects, such as a dry mouth or sedation, and those that may feel like a worsening of the illness – such as feeling more nervous or feeling strange and unreal, or even hearing voices. These latter side effects are the ones that need careful judgement and may pose the greatest risks.
The obvious side effects of antidepressants
Sedation
Many antidepressants, especially amitriptyline, trimipramine, mirtazapine and trazodone, are very sedative when first taken, but almost all can be somewhat sedative. This sedation is similar to the effect of some of the older antihistamines. Just as with the antihistamines, about one-third of people who take these drugs are clearly sedated, while two-thirds are either slightly sedated or not sedated 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 is compromised.
In the case of the SSRIs, there may be a paradoxical coexistence of feeling drowsy or fatigued, along with an inability to sleep. Even more clearly with the SSRIs, some people may be drowsy while others are unable to sleep, so that for some the dose of an SSRI should be given in the morning and for others in the evening.
Arousal
In some people, rather than sedating, antidepressants may arouse and 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. This is a problem more likely to happen with antidepressants acting on noradrenergic systems, such as desipramine, nortriptyline or reboxetine.
Monoamine oxidase inhibitors (MAOIs) are more likely than tricyclics to cause arousal. For this reason they are usually given in the morning rather than at night. However, MAOIs may be heavily sedating in some cases and have to be given last thing at night.
In the case of the SSRIs, a proportion of people are stimulated by them, whereas others are clearly sedated. Even more unusually, the SSRIs sometimes 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 antidepressants 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.
For the most part, a dry mouth is a relatively minor inconvenience. It can, however, be a more serious problem for some individuals, as saliva protects against tooth decay and its lack may aggravate dental problems.
It has been traditional to put dry mouth down to the anticholinergic properties of antidepressants. However, the SSRIs, which have been supposed to have little or no anticholinergic effects, also produce a dry mouth.
Fainting
Tricyclic antidepressants, MAOIs and mirtazapine all lower blood pressure. For most of us, abrupt changes in posture after getting out of bed or standing up from a chair can produce a feeling of faintness or a hint of seeing stars. On treatment, these postural changes may be exaggerated so that a minor change of posture may cause a significant drop in blood pressure, leading a subject to topple over and potentially to serious injury. This is a greater hazard in older individuals, for whom changes in posture are more likely to drop blood pressure anyway.
Palpitations
Palpitations are one of the more unsettling effects of an antidepressant. Finding one’s heart beating irregularly or thumping in one’s chest is alarming. Despite being alarming, palpitations are usually harmless. They may simply stem from the heart trying to compensate for a drop in blood pressure by putting out more blood. But all antidepressants can also cause direct cardiac effects, which may be a real hazard for individuals with pre-existing heart trouble, and for this reason, while ordinarily harmless, palpitations should be assessed rather than dismissed.
Urinary difficulties
Most antidepressants can cause trouble with urination. In the mildest cases, the subject will be aware that there is a slight delay before passing water. 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 only men, but they also affect women – even young women. Occasionally the problem may be more marked to the point of having clear difficulty in passing water or even urinary retention. This latter is most common in older men with enlarged prostate glands.
Almost all books and articles put this side effect down to the anticholinergic properties of tricyclic antidepressants. However, there also appears to be a serotonergic input to the bladder, so that SSRIs may lead to something of an increase in bladder capacity and antipsychotics that block S2 receptors, such as clozapine, may lead to a decrease. With the release of reboxetine, which has no anticholinergic effects, it has become clearer that the greatest problems stem from the action of these drugs on the noradrenergic system. Duloxetine, which inhibits both catecholamine and serotonin uptake, is also marketed as a bladder stabiliser, and atomoxetine (see Ch. 8), now used for attention deficit/hyperactivity disorder (ADHD) was also investigated as a bladder stabiliser.
Sweating
It is not uncommon for antidepressants to produce sweating. This is particularly common in hot weather. It may be most noticeable at night, leading to people waking up to find their sheets drenched. Increased perspiration may also be a feature of the serotonin syndrome (see below).
Shake or 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.
Essentially, antidepressants – and in particular the SSRIs – can cause all the problems that the antipsychotics cause, from dyskinesias to dystonias, to akathisia and parkinsonian features (see Ch. 3). All these problems are likely to be more obvious when SSRIs are combined with antipsychotics, lithium, valproate, analgesics or oral contraceptives.
Twitch or jerk
All antidepressants can 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 it happens in up to 10% of takers. It may be commoner with drugs active on the serotonin system. It usually stops on switching to another treatment.
Tooth-grinding (bruxism) and jaw-locking (trismus)
Another rarely described side effect is tooth-grinding. Many of us grind our teeth during sleep. Some antidepressants, in particular the SSRIs, may lead to tooth-grinding during the day. This 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 to a grinding down of the teeth.
There may be two distinct components to the problem: 1) abnormal movement of the jaw (a dyskinesia) and 2) an increase in tone of the jaw muscles (dystonia). In mild forms, this increased tone may be painful and, confusingly, may be experienced simply as a pain in the jaw area. In more severe forms, it can lead to lockjaw (trismus). The problems may also affect the throat, and may be experienced as an acute sore throat (pharyngitis), leading the taker to believe they have a throat infection. In other cases there may be difficulty swallowing, as though the throat is constricted. Another variation on the phenomenon is forced yawning.
Although this problem is rarely described, up to 50% of the takers of an SSRI may experience these problems during the first week of treatment. Tooth-grinding is the more likely to persist. This has the potential to lead on to tardive dyskinesia and perhaps should lead to treatment being halted.
Headache
Headaches are a common feature of depression and therefore it may be difficult to be sure whether an antidepressant has caused them. An antidepressant headache is usually different from the one found in depression. Typically, antidepressants give a muzziness or feeling of painful fullness rather than the aching, tension-type headache that most of us have had at some point or other. It may not be possible to distinguish these headaches, however, and 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 – headaches that have a throbbing, pulsating character, usually affect 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 because most of these drugs act on the serotonin system, which regulates blood flow through the head and brain. Headaches are almost certainly harmless. The issue is whether they are too uncomfortable to put up with, rather than whether they are serious.
Headaches may be more serious in individuals who are on MAOIs and who have eaten food containing tyramine (see The cheese effect, below), or in individuals taking lithium. Headaches are also likely to be more serious when they occur in someone taking combinations of treatments, such as antidepressants and antipsychotics, or either of these combined with lithium.
5.1.1. Blurred vision
A further side effect of most antidepressants is blurred vision. This is particularly likely to happen on tricyclics, which have the most marked anticholinergic effects, but eyesight disturbances also happen with SSRIs. 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. Any change of glasses should usually be deferred until after the drug has been discontinued.
Occasionally, individuals prone to glaucoma will have their condition exacerbated by treatment, making it 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. This, however, is a rare occurrence.
Weight gain
Depression often leads to a loss of appetite and weight. Successful treatment can therefore be expected 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 5–10kg for reasons that are not fully understood but that are drug induced. Weight gain may be aggravated in individuals who are also taking lithium and antipsychotics.
Until recently there was no option as regards the issue of weight gain because all the antidepressants were liable to cause the problem. The SSRIs, however, do provide a short-term option. In the short term, SSRIs have an appetite-suppressing property. In some cases they may cause nausea and even vomiting. The nausea generally subsides within a few days, but a mild suppression of appetite, as opposed to the mild increase that may be brought about by other antidepressants, may remain. Over time, however, weight gain on SSRIs often occurs and may, indeed, be dramatic.
While weight gain may seem like an obvious side effect of drug treatment, many individuals seem to be unaware that their drugs may be causing the weight gain and, accordingly, they may try to diet strenuously, abetted by their primary care 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 other agents. Up to 25% of people who take these drugs may feel as though they are 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. This seems to be a greater problem in Asian populations.
Rashes and infections
All drugs may cause idiosyncratic hypersensitivity reactions. The commonest sign of such a reaction is a skin rash. Skin rashes for the most part are not harmful and go quickly once the drug has been stopped. A more serious problem is recurrent fevers, with a sore throat and painful mouth. It may be necessary to take a blood test to check the white blood cell count to establish what is happening. Treatment may have led to a lowering of the white cell count, which predisposes to infection, especially in the elderly.
THE AMBIGUOUS SIDE EFFECTS OF ANTIDEPRESSANTS
Dissociative side effects
The dissociative side effects of antidepressants include depersonalisation, derealisation and a number of other experiences that may be severe enough to produce frank confusion. The danger of these dissociative experiences lies in the fact that they may be interpreted by either the person taking the antidepressant or others as evidence that the illness is getting worse or that brain damage of some sort has been caused. If misinterpreted, such reactions can lead to suicide (see below). This risk, and the fact that a drug causing such reactions is most unlikely to cure depression, provide grounds for switching treatment.
Depersonalisation
Depersonalisation refers to an 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 in other stressful situations where part of us seems to be functioning automatically and not under full control. Depersonalisation and derealisation are dissociative reactions that are relatively common on antidepressants.
Derealisation
Derealisation refers to a similar set of feelings and perceptions to those seen in depersonalisation, but in this case they apply to the world rather than to the self. This is 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 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. Like palpitations, these are very unsettling rather than directly dangerous experiences.
Other dissociative experiences
• A feeling that time is standing still
• Déjà vu experiences
• Prominent nightmares or lucid dreaming – where the dreamer feels awake
• Out-of-body experiences
• Amnesia. In some cases an individual on antidepressants may find their memory clearly impaired. Subsequently, on discontinuing the drug, they may find it difficult to remember things that happened to them while they were on treatment
• Auditory or visual hallucinations. These are more likely in the elderly but can happen to anyone. They are not serious. They clear up once the drug is discontinued. The biggest problem arises if the experience prompts someone to think that their illness must be getting worse because ‘everyone knows voices are a sign of lunacy’.
Confusion or disorientation
Also rare and serious is the occurrence in some individuals of confusion. This may be more obvious in older people but probably occurs in all age groups and is 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. One step further along this path lies confusion, when it becomes obvious to others that something is not quite right. An affected subject may get to the stage of being disoriented and, as a consequence, quite agitated in a way that makes them a risk to themselves or to others.
