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Medication

1.0 INTRODUCTION

The use of medication to 'treat' borderline personality disorder is, to say the very least, controversial. This terminology would imply it is possible, and desirable, to treat personality itself.

There are a number of general concepts that should be borne in mind when considering medications:

1. Medication should ideally be used in the context of an overall care-plan which includes psychotherapy. It is recognised that only psychotherapy can produce the interpersonal changes that are needed for the eventual cure of borderline problems. However medication can reduce the severity of perceptual disturbances, emotional turmoil and impulsive behaviour and can allow the BP to engage more productively in psychotherapy.

2. Borderline personality disorder is a multidimensional syndrome and no one medication is effective across the full spectrum of symptoms. Individual symptoms need specific medications.

3. Borderline personality disorder is a chronic disorder and at best, medication can offer only modest symptom relief.

4. At the time of writing good, impartial evidence for the efficacy of medications is lacking. Any information included herein may be superseded relatively quickly. However, the situation that exists in Britain is that psychotherapy is often not readily available to patients with BPD. Consequently, the vast majority of patients are treated by their psychiatrist or general practitioner, who are hard-pressed for time and resources and frequently conceive medication to be the best, and sometimes only, option.

2.0 ANTIDEPRESSANTS

Some symptoms of BPD are common to those observed in depression e.g. emptiness, hopelessness, lack of energy etc. Of course, it is possible for depression to exist concurrently with BPD and many of these symptoms are improved with antidepressant treatment. They may also be used to treat such symptoms as impulsive aggression, self-mutilation, anger and labile mood. They may also be used to treat the symptoms of anxiety, reduce panic attacks and alleviate the painful feelings, dysphoria, described by many sufferers.

All antidepressant medications may take several weeks before they have any noticeable effect on mood. It is important to persevere with treatment, at a recognised therapeutic dose, and give them an opportunity to have an effect.

2.1 TRICYCLIC ANTIDEPRESSANTS (TCA)

These older generation antidepressants are very effective and exert their effect by increasing levels of the neurotransmitters serotonin and noradrenaline (norepinephrine) in the brain. However, they have a number of common, unpleasant side-effects (which may appear before mood improves) and are very toxic in overdose. Sometimes discontinuation effects are experienced if the medication is stopped suddenly. In order to avoid this problem, a gradual tapering of the dose is recommended.
eg amitryptyline (Tryptizol®), clomipramine (Anafranil®), dothiepin (Prothiaden®), lofepramine (Gamanil®) and many others.

SIDE EFFECTS: Drowsiness, constipation, dry mouth, blurred vision, weight gain.

2.2 SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRI)

This newer group of antidepressants all act to increase the brain levels of the neurotransmitter serotonin. The side effect profile is generally more acceptable and they are safe in overdose. They can be associated with a paradoxical increase in anxiety for the first week or so, but this should pass. There have also been many reports of a withdrawal (discontinuation) syndrome, especially with paroxetine. This may be avoided by a very gradual reduction in dose. They are taken as a single daily dose.
eg fluoxetine (Prozac®), paroxetine (Seroxat®), citalopram (Cipramil®), sertraline (Lustral®), fluvoxamine (Faverin®).

SIDE EFFECTS: Nausea and vomiting, insomnia, sexual dysfunction, loss of appetite

PAROXETINE: please be aware of the recent developments in relation to this drug and seek advice if you are at all concerned. Further information is available here. The relevant details are in "paraxoetine and pediatric and adolescent clinical trial data."

2.3 MONOAMINE OXIDASE INHIBITORS (MAOI)

This is an older group of drugs that are used much less routinely. They may still be used to treat atypical depression (ie excessive sleeping, increased appetite, weight gain) and depression associated with obsessional thoughts, panic attacks and anxiety. They are toxic in overdose and are subject to a number of dietary restrictions and interact with a number of commonly available medicines.
eg isocarboxazid (Marplan), phenelzine (Nardil), tranylcypromine (Parnate)

SIDE EFFECTS: Dizziness/faintness on standing (postural hypotension), drowsiness, dry mouth, constipation.

2.4 OTHER ANTIDEPRESSANTS

As these medications are relatively new to the scene, controlled studies are few and far between. Individual case reports have shown that some of these drugs are effective in certain individuals, though these effects may not be reproducible. The usual processes of testing new drugs against existing ones have not yet been performed, but trials are underway; some of more dubious standards than others.

2.4.1 Venlafaxine (Efexor®) is described as a serotonin and noradrenaline re-uptake inhibitor (SNRI). It is essentially a "cleaned up" version of a tricyclic antidepressant that lacks the sedative properties and other common side effects of the TCAs. It is also safer in overdose. It needs to be taken twice daily as a tablet, but a long acting capsule is available that only needs to be taken daily. The capsule form may cause less nausea initially.

Some trials have suggested that it is superior to other antidepressants in treating resistant depression and also that it may be more effective than SSRIs, particularly in the in-patient setting.

It's side effects are similar to those of the SSRIs ie nausea, headache etc. Excessive sweating has been reported and it has a strong withdrawal syndrome. Occasionally, high doses of venlafaxine (ie greater than 200mg a day) can cause an elevation in blood pressure; therefore, blood pressure monitoring is advised if higher doses are being taken.

2.4.2 Reboxetine (Edronax®) is a selective noradrenaline re-uptake inhibitor (NARI). It needs to be given twice daily. It may possibly be more effective in severe depression and it may improve social functioning. The most common side effects are dry mouth, constipation, sweating and insomnia. It is not sedative and does not potentiate the effects of alcohol.

2.4.3 Mirtazepine (Zispin®) is classified as a NaSSA, or noradrenaline and specific serotonin antidepressant. It's most noticeable effect is drowsiness, which may help people who suffer from insomnia. For this reason, it is usually given as a single dose at bedtime. In addition, weight gain as a result of increased appetite is common. Again, this may be advantageous if loss of appetite is a predominant symptom. A serious, though very rare side effect of mirtazepine, is a lowered white blood cell count. Patients taking this medication should note than any sign of infection, eg sore throat etc should be reported to a doctor. On a more positive note, it is less likely than most other antidepressants to interfere with sexual functioning. It is sometimes added to treatment with an SSRI, to enhance their antidepressant effect.

2.4.4 Nefazodone (Dutonin®) is related to one of the older types of medications (trazodone) and may be described as a serotonin receptor modulator (SRM). It increases the transmission of both the neurotransmitters serotonin and noradrenaline. It is a sedative-type antidepressant and has a specific effect in improving sleep patterns. It needs to be taken twice daily, and the dose must be gradually increased to the required dosage. A "starter pack" is available to make this increasing dosage simpler to take. Sexual side effects are reported much less commonly with nefazodone than other antidepressants.

3.0 ANTIPSYCHOTICS (MAJOR TRANQUILISERS, NEUROLEPTICS)

These medications are probably the most studied in the treatment of BPD and have been used successfully, over a number of years, to alleviate some of the symptoms of BPD. Some examples of symptoms reported to be improved are anger, irritability, hostility, dissociative symptoms, self-destructive impulses, hallucinations, paranoid thoughts and also intense anxiety. Despite their alternative name (tranquilisers), these medications are not addictive.

They exert their main effect by altering the effect of another of the brains neurochemicals, dopamine.

3.1 OLDER GENERATION NEUROLEPTICS / TYPICAL ANTIPSYCHOTICS

These medications have been used successfully for many years to treat various psychotic illnesses. They have a number of very unpleasant side effects, which limit their use now, as more acceptable alternatives are available. However, they are still very widely used and effective treatments are available to relieve some of the side effects. The main advantage they offer over more recent developments is that some are available as a depot injection. This allows the medication to be administered as an intramuscular injection once every few weeks. This eliminates the need to remember to take tablets every day. They may also be used in hospital settings to achieve rapid control of a difficult situation.
eg chlorpromazine (Largactil®), flupenthixol (Depixol®), fluphenazine (Moditen®, Modecate®) haloperidol (Serenace®, Haldol®), trifluoperazine (Stelazine®) and others.

SIDE EFFECTS: As mentioned above, these treatments frequently cause uncomfortable side effects (technically termed extra-pyramidal side effects). These include a sensation of inner restlessness or agitation, involuntary movement disorders and rigidity. The most concerning problem is known as tardive dyskinesia - a writhing of the tongue and mouth, which if develops, may persist even after the medication is discontinued. The problem is more common with higher doses given over a long time. Most of these symptoms can be alleviated with another type of medication (eg procyclidine).Other, less serious side effects include drowsiness, constipation, dry mouth, weight gain, blurred vision and altered menstrual cycle.

3.2 NEWER GENERATION NEUROLEPTICS / ATYPICAL ANTIPSYCHOTICS

There has been a lot of coverage in the media recently that patients should receive these newer medications as first line treatment. As they do not have the extra-pyramidal side effects of the older drugs, they are much more acceptable to patients and more likely to be taken regularly. Although they vary markedly in their chemical make up, they all produce their effect by affecting both dopamine and serotonin in the brain.

There have been individual case reports that clozapine may reduce self-harming behaviours. However, it is not commonly used, as regular blood tests must be performed to prevent serious infections developing.
e.g. olanzapine (Zyprexa®), risperidone (Risperdal®), quetiapine (Seroquel®), amisulpiride (Solian®), clozapine (Clozaril®)

SIDE EFFECTS: weight gain, drowsiness, excessive salivation, constipation, low blood pressure are amongst just some of the wide ranging reported side effects of these drugs.

4.0 MOOD STABILISERS / ANTI MANIC DRUG

Medications that come under this heading have primarily been investigated for the treatment of manic-depression (bipolar affective disorder). However, one of the most commonly reported symptoms of BPD are intense mood swings, which have been alleged to improve with mood stabilising treatments. Explosive anger, aggression and self-mutilation may also be diminished with mood stabilisers. Symptoms such as anger may occur as part of the clinical depression picture. In such instances, mood stabilisers may have a better effect than antidepressants, which can cause an increase in aggression, particularly during the early stages of treatment. They are also combined with antidepressants to augment their efficacy.

4.1 LITHIUM (Priadel®, Camcolit®)

Lithium has been used as a medication since the 1960s and much is known about its effects, although it's precise mechanism of action is still unclear. A number of reputable trials have indicated lithium as effectively minimising mood swings in BPD patients. It has been reported to induce "reflective delay", i.e. reducing impulsivity and giving more consideration to ones actions. Despite it's efficacy, it is a very toxic substance, which must be very closely monitored by regular blood tests to prevent blood levels becoming dangerously high. It can interact with other medications to produce concentrations above the acceptable range. It is not uncommon that problems of the thyroid gland develop which may require replacement thyroxine treatment. Routine testing of the thyroid gland, kidneys and bone chemistry are also performed.

SIDE EFFECTS: Tremor, nausea, diarrhoea, excessive thirst, frequent urination and weight gain are common, non-serious side effects that may improve with continued treatment. Signs of excessive amounts of lithium in the blood are unsteadiness, confusion and blurred vision.

4.2 CARBAMAZEPINE (Tegretol®)

This is the most commonly used alternative to lithium, as it is much safer and requires less blood sampling. A number of trials have been conducted which have cited that it reduces the frequency and severity of aggressive outbursts. The incidence of suicide attempts has been shown to be reduced, and the intensity of anxiety and anger was improved.

SIDE EFFECTS: Drowsiness, double vision, dizziness, nausea and vomiting are the most commonly reported side effects. There is a very slight risk of the white blood cell count being seriously reduced (agranulocytosis), preventing the ability to fight infections. Although this risk is slight, it is important to mention any sign of infection to your doctor.

4.2.1 OXCARBAZEPINE (Trileptal®)

As yet, oxcarbazepine has not been studied in the treatment of BPD. However, as it is related to carbamazepine and is thought to be of a similar efficacy, it is likely that it will be tried in patients who are unable to tolerate carbamazepine due to unpleasant side effects.

4.3 SODIUM VALPROATE (Epilim®)

Again, used as an alternative to lithium. A very small study suggested that valproate effectively treated impulsive aggressive behaviour in BPD, which had not responded previously to an SSRI antidepressant. It is a relatively safe drug, which is generally well tolerated among patients. There is a slow release version, which needs only to be taken once daily.

SIDE EFFECTS: Increased appetite, weight gain, nausea, stomach irritation and drowsiness are the most common side effects. Very rarely, the liver can be affected. Regular liver tests are performed at the beginning of treatment.

4.3.1 VALPROATE SEMISODIUM (Depakote®)

This is a newly launched drug which converts in the body to valproate (as above). At present, it is thought to have very little advantage, if any, over the original version. Obviously it is too early to comment as to whether it improves the functioning of BPD sufferers.

4.4 OTHERS

ie lamotrigine (Lamictal®), clonazepam (Rivotril®), gabapentin (Neurontin®), tiagabine (Gabitril®), topiramate (Topamax®) and vigabatrin (Sabril®)

There is growing interest in the use of these agents as mood stabilisers and the list of individual case reports is ever increasing. However, as larger, controlled trials have not been performed, there is no definitive decision as to whether they are effective or not.

5.0 ANXIOLYTICS AND HYPNOTICS (MINOR TRANQUILISERS, SLEEPING TABLETS)

Anxiety and insomnia can often be quite disabling and distressing features of BPD. In many cases, therapy of some description is the most ideal, long term solution. However, during periods of increased stress, BPs may find the crisis too difficult to cope with and medication may be used on a short term basis. As mentioned earlier, SSRIs are often used to control symptoms of anxiety and long term use, if necessary, is a safer and more desirable option

5.1 BENZODIAZEPINES

eg diazepam (Valium®), nitrazepam (Mogadon®), temazepam, lorazepam (Ativan®) and others.

Historically, these agents have been used to treat anxiety and insomnia as a first line treatment. However, their potential for dependence, withdrawal effects and abuse have led to them becoming a less favoured approach. All available benzodiazepines reduce anxiety at low doses and induce sleep at higher doses, and are thus essentially all the same. The differences are in their length of action. For the treatment of anxiety, a product with a long duration of action is preferable as they are less likely to cause withdrawal problems. Benzodiazepines with a shorter duration of action are preferred to treat sleeplessness as this is less likely to cause a "hang-over" effect the following day, which may impair daytime performance.

Their use is not encouraged in patients with BPD as they may cause a paradoxical increase in hostility and aggression. They are also known to be disinhibiting, which may exacerbate behavioural impulsiveness. They can trigger flashbacks and in the long term, may worsen depression.

Benzodiazepines are both physically and psychologically addictive. This leads to their most troublesome effect; an inability to stop taking them if they have been taken for a long time. Withdrawal effects of benzodiazepines are characterised by insomnia, anxiety, loss of appetite and body weight, tremor, perspiration and ringing in the ears. For this reason, if a benzodiazepine has been taken regularly for a long time (ie longer than the recommended maximum of three weeks), it should be withdrawn very slowly, with additional support from a doctor or therapist. These effects are unlikely to happen if taken only occasionally.

SIDE EFFECTS: In addition to those mentioned above, benzodiazepines can cause dizziness, confusion and unsteadiness on the feet.

5.2 BUSPIRONE (Buspar®)

This is a unique product for the treatment of anxiety states (with or without accompanying depression). It seems to increase levels of dopamine and noradrenaline, whilst decreasing the action of serotonin and acetylcholine. However, it's full mode of action is not known. When used in addition to an SSRI, it may counteract the problematic side effects caused by these drugs. It may take up to two weeks for any effect to show, and whilst it is not addictive, it is only recommended for short term use. It is therefore not suitable for treating acute anxiety states. It does not produce dependence and there is no withdrawal reaction on discontinuation of therapy. Doses higher than those published may be required to produce a noticeable effect.

SIDE EFFECTS: Dizziness, headache, nausea, restlessness, "light headedness" and excitement are most likely to occur early on in treatment.

5.3 OTHER HYPNOTICS

ie zopiclone (Zimovane®), zolpidem (Stilnoct®), zaleplon (Sonata®).

These newer sleeping tablets have very differing chemistry, but they are grouped together as they are all rapid acting, non-benzodiazepine drugs. They are claimed to be non-addictive and dose increases are not supposed to be required, however in practice people do report difficulty coming off them and needing higher and higher doses. Zaleplon is an ultra short acting drug that can be taken in the middle of the night if early waking is a problem. There is likely to be no hangover effect as a consequence of its rapid action. If necessary, two doses can be taken in the same night. Zopiclone and zolpidem have been shown to increase overall sleep duration.

SIDE EFFECTS: Headache, memory disturbances, metallic taste (zopiclone), dizziness and light-headedness are most likely to be encountered.

5.4 BETA-BLOCKERS

Drugs such as propranolol (Inderal®) and oxprenolol (Trasicor®) are mainly used to treat heart and blood pressure problems. However, they can help control some of the more physical signs of anxiety such as tremor, shaking, racing heart beat, sweating. These symptoms can induce further anxiety and a vicious circle is set up. Beta-blockers are effective at breaking this cycle. They are also effective at relieving the sensation of restlessness caused by some of the older generation antipsychotics. As they are not addictive, they are suitable for long term use.

SIDE EFFECTS: Fatigue, cold fingers and toes, nightmares and sexual dysfunction are relatively common occurrences.