The person with depression
CASE AIMS
After examining this case study the reader should be able to:
• Identify the parts of the brain involved in mood regulation.
• Outline the neurotransmitters thought to be involved in pathophysiology of depression.
• Demonstrate an understanding of the reason for prescribing and the mode of action of citalopram.
• Demonstrate an understanding of the reason for prescribing and the mode of action of venlafaxine.
• Discuss the role of the nurse in monitoring and caring for a patient receiving selective serotonin reuptake inhibitors.
• Describe what is meant by serotonin syndrome.
• Discuss the role of the nurse in giving advice about discontinuation syndrome in a service user who suddenly stops their medication.
CASE
Pierre is an extremely successful teacher who is well respected by his peers. Although he has always been thought of as gregarious, outgoing and fun-loving, for the past couple of months he has not been feeling quite himself. He no longer enjoys things they way he used to and he feels a profound sense of sadness on most days; so much so that he feels utterly hopeless about his future. To make matters worse, Pierre’s previously healthy appetite has evaporated and he often finds himself waking up very early in the morning and unable to fall asleep again. Although Pierre has always enjoyed hockey and weight training, lately he has found that he just doesn’t have the energy to do much of anything. At work, he has been scraping by and cannot seem to concentrate or make quick decisions, both of which have conspired to send his self-esteem and sense of worth into a tailspin.
His friends, co-workers and family are growing increasingly concerned as he is returning phone calls and emails less frequently, and seems very withdrawn and despondent. One evening Pierre finds himself working late and becomes very tearful because he believes he cannot cope with life any more. The next day his wife persuades him to go to the GP who diagnoses depression and prescribes citalopram 20mg once daily. The GP also makes an urgent referral to a psychiatrist and asks him to come back in a week to see her.
1 What parts of the brain are thought to be involved in regulating Pierre’s mood?
2 Which neurotransmitters are thought to be involved in the causation of his depression?
3 Explain the mode of action of citalopram in helping Pierre become less depressed
Pierre has now been on citalopram for a number of weeks and reports to the psy-chiatrist that he has become increasingly anxious and seems unable to relax or rest. He is also complaining of insomnia. The psychiatrist decides that these are side-effects from his current medication and changes his prescription to venlafaxine 75mg daily in two divided doses.
4 Why has Pierre now been prescribed venlafaxine?
5 Outline the role of the nurse in monitoring and caring for Pierre while taking his medication
Pierre is now feeling much better and has returned to work. He visits his GP who has now taken over his care. He says that he does not need the ‘tablets’ any more and has not taken any for a couple of days.
6 What problems could occur now that Pierre has decided suddenly to stop his venlafaxine because feels he is able to cope without tablets?
7 What advice could be given to Pierre in order to prevent or reduce any symptoms of discontinuation of his medicines?
ANSWERS
1 What parts of the brain are thought to be involved in regulating Pierre’s mood?
A Pierre’s limbic system is not a structure, but a series of nerve pathways incorporating structures deep within the temporal lobes, such as the hippocampus and the amygdala. Forming connections with the cerebral cortex, white matter and brainstem, the limbic system is involved in the control and expression of mood and emotion, in the processing and storage of recent memory, and in the control of appetite and emotional responses to food. We can see from the case study that Pierre has lost interest in his food. All these functions are frequently affected in depression and the limbic system has been implicated in the pathogenesis of depression. The limbic system is also linked with parts of the neuroendocrine and autonomic nervous systems, and some neurological disorders, such as anxiety, are associated with both hormonal and autonomic changes (Tortora and Derrickson 2009).
2 Which neurotransmitters are thought to be involved in the causation of his depression?
A Evidence now strongly supports the theory that depression has a biologic basis and that certain brain chemicals and neural pathways responsible for regulating mood and associated behaviours are altered. The basic biological causes of depression are strongly linked to abnormalities in the delivery of certain key neurotransmitters (chemical messengers in the brain).
SEROTONIN
Perhaps the most important neurotransmitter in depression is serotonin. Among other functions, it is important for feelings of well-being. Pierre no longer enjoys things the way he used to and feels a profound sense of sadness nearly every day. Indications are that serotonin improves a person’s ability to pick up emotional cues from other people, which is important for healthy relationships. People deficient in serotonin are less likely to take risks for high rewards than those with normal levels (Cowen 2002).
OTHER NEUROTRANSMITTERS
Other neurotransmitters possibly involved in depression include acetylcholine and catecholamines, a group of neurotransmitters that consists of dopamine, norepinephrine and epinephrine (also called adrenaline). Corticotrophin-releasing factor (CRF), which is believed to be a stress hormone and a neurotransmitter, is thought to be involved in depression and anxiety. Increased CRF concentrations appear to interact with serotonin and have been detected in patients with either depression or anxiety (Kalia 2005).
3 Explain the mode of action of citalopram in helping Pierre become less depressed
A The mechanism of action of citalopram as an antidepressant is presumed to be linked to potentiation of serotonergic activity in the CNS, resulting from its inhibition of CNS neuronal reuptake of serotonin. In vitro and in vivo studies in animals suggest that citalopram is a highly selective serotonin reuptake inhibitor (SSRI) with minimal effects on norepinephrine and dopamine neuronal reuptake. Tolerance to the inhibition of serotonin uptake is not induced by long-term (14-day) treatment of rats with citalopram (Rang et al. 2011).
4 Why has Pierre now been prescribed venlafaxine?
A Venlafaxine is an antidepressant in a group of drugs known as selective serotonin and nor-epinephrine reuptake inhibitors (SSNRIs). Even though its side-effect profile is similar to that of SSRIs, venlafaxine seems to have relative freedom from the side-effects associated with SSRIs (fluoxetine, sertraline, paroxetine, fluvoxamine). It is hypothesized that the action of the venlafaxine molecule on both serotonin and norepinephrine will cause venlafaxine to be a successful antidepressant for some people who have not responded to treatment with SSRIs. As venlafaxine and its active metabolite have relatively short half-lives (4 hours and 11 hours respectively), venlafaxine should be administered in divided doses, two or three times a day (BNF 2012).
5 Outline the role of the nurse in monitoring and caring for Pierre while taking his medication
A
• Pierre may feel nauseous, therefore simple advice, such as eating little and often, may be of value. Also, eating simple foods such as dry toast rather than rich foods may be something the service user may wish to contemplate.
• Another common side-effect of these types of medicine is a dry mouth. Therefore, reinforcing the importance of drinking adequate fluids over a 24-hour period will be important (usually 3L). Another tip is to suggest chewing low-sugar gum or sweets in order to promote saliva production.
• You would need to monitor Pierre’s vital signs, especially pulse and blood pressure, parti-cularly when initiating treatment. You would need to report any change in Pierre’s senses, particularly impending syncope. Syncope is a transient loss of consciousness caused by transient global cerebral hypoperfusion, characterized by rapid onset, short duration and spontaneous complete recovery (European Society of Cardiology 2009). In order to avoid Pierre developing syncope you would avoid abrupt changes in position, monitor vital signs (especially blood pressure) and remind him to report any blood pressure readings (e.g. lower than 80/50mmHg).
• If Pierre suffered from drowsiness then the medicine could be taken at bedtime to aid in sleep and minimize daytime drowsiness. Advise Pierre to ensure he feels his reactions are normal before driving, operating machinery or doing any other jobs which could be dangerous if he were not fully alert. Tell him to avoid alcohol, as this will increase any feelings of drowsiness (BNF 2012). Any sedative effect is likely to be greatest in the first month of treatment, or on increasing the dose. Drugs such as paroxetine have been associated with the highest rate of drowsiness (Greenstein 2009).
• You should monitor Pierre’s mental and emotional status. There has been shown to be an increase in suicidal ideation for some time now in children and adolescents who have been prescribed SSRIs/SSNRIs (Hetrick et al. 2007). Although this correlation is rather more unclear in the treatment of adults, you should be risk-assessing, particularly as the therapeutic benefits may be delayed. If severely depressed, and being treated as an outpatient, the service user should have no more than seven days of medication supplied in case of self-harm (DH 2004).
• Part of your role is to observe Pierre for signs and symptoms of improved mood, keeping in mind that it may take two to four weeks to achieve therapeutic effectiveness (the risk of suicide may increase as energy levels rise). The National Institute for Health and Clinical Excellence (NICE) (2009) suggests that advice should be given to the service user with depression about the potential for increased agitation, anxiety and suicidal ideation in the initial stages of treatment. As a result you should be actively seeking out these symptoms and reporting them to the medical staff or GP. Pierre should be advised that it may take two to four weeks for his mood to improve. He should be reassured that you will always have time to listen and talk to him, especially if he wishes to report any feelings of suicide (Barber and Robertson 2012).
• You should observe Pierre for serotonin syndrome in SSRI use. This is an adverse drug reaction to medicines that increase the amount of serotonin in the CNS. It can occur as a consequence of normal therapeutic drug use, self-poisoning or drug interactions (Boyer and Shannon 2005). Generally you should be looking for three sets of symptoms in Pierre: agitation and hypervigilance; increased sweating or heart rate; neuromuscular abnormalities such as temor.
• If serotonin syndrome is suspected, discontinue the drug and initiate supportive care. Respond according to any local emergency department protocols. For example, if the service user has recently ingested or taken a large overdose, then activated charcoal may help to prevent absorption. Supportive measures such as the giving of IV fluids and controlling agitation with benzodiazepines may also be used by the A&E department. One of the problems with serotonin syndrome is that other medicines can cause it to happen. Therefore part of the nurse’s role is to educate Pierre to be vigilant about drug combinations and to inform health care workers that he is taking SSRIs (Houlihan 2004).
• According to Rottmann (2007) the use of SSRIs/SSNRIs can also be associated with disruption of the action of the antidiuretic hormone in the body, which affects the individual’s homeostasis. This may lead to the syndrome of inappropriate antidiuretic hormone secretion (SIADH), which is characterized by hyponatremia, a potentially fatal condition that is typically asymptomatic until it becomes severe. SIADH is more likely in some populations, including people who are elderly or who take diuretics. Pierre’s serum sodium levels may need to be monitored closely, especially if he is at a higher risk.
• Sexual dysfunction could be a real problem for Pierre, so developing an open and honest relationship with him is important. He needs to trust you enough to be able to discuss this type of problem without fear of embarrassment (Rang et al. 2011).
• SSRIs/SSNRIs are associated with an increased risk of bleeding, especially in older people or in people taking other drugs that have the potential to damage the GI mucosa or interfere with clotting. Therefore, Pierre should be educated to avoid taking his SSRI medication with aspirin, warfarin or non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or naproxen. He should be reassured that if he is already taking medications that may cause GI bleeding, and if no suitable alternative to an SSRI can be found, the doctor may advise him to take another medicine to protect the lining of the gut – for example omeprazole (NICE 2009).
6 What problems could occur now that Pierre has decided suddenly to stop his venlafaxine because he feels he is able to cope without tablets?
A Discontinuation symptoms typically arise within days after stopping medication, particularly if it was stopped abruptly. After some people stop taking SSNRIs, they experience a variety of symptoms including:
• a flu-like reaction;
• headache;
• GI distress;
• faintness;
• strange sensations of vision or touch.
This common phenomenon is known as discontinuation syndrome. It may also be known as SSNRI withdrawal syndrome (Michelson et al. 2000). Other symptoms of discontinuation are similar to discontinuing other antidepressants, including:
• irritability;
• restlessness;
• headache;
• nausea;
• fatigue;
• excessive sweating;
• dysphoria;
• tremor;
• vertigo;
• irregularities in blood pressure;
• dizziness;
• visual and auditory hallucinations;
• feelings of abdominal distension and paraesthesia.
Other non-specific mental symptoms may include:
• impaired concentration;
• bizarre dreams;
• delirium;
• agitation;
• hostility;
• worsening of depressive symptoms.
7 What advice could be given to Pierre in order to prevent or reduce any symptoms of discontinuation of his medicines?
A
• Pierre should be advised not to suddenly stop taking his medication. People may stop their medicine abruptly for various reasons, including feeling better or experiencing unpleasant side-effects, as well as simply forgetting to renew a prescription. However, as noted above, stopping some medicines abruptly can cause discontinuation or withdrawal symptoms.
• Pierre should be encouraged to talk to his doctor. He should be able to voice any concerns he has so that he does not attempt to stop medicating without help. It should be a collaborative venture between the service user and the doctor. In physical conditions, communication between the service user and the physician within the consultation has also been shown to play an important role in influencing treatment adherence (Hunot et al. 2007).
• It is important that the service user be advised not to discontinue if they are under a lot of stress, not sleeping well, not eating nourishing foods, or not sticking to a consistent schedule. Under these conditions stopping their medicine successfully may be unrealistic and could increase anxiety and depression, making stopping even harder.
KEY POINTS
• The limbic system is involved in the control and expression of mood and emotion, in the processing and storage of recent memory, and in the control of appetite and emotional responses to food.
• The basic biological causes of depression are strongly linked to abnormalities in the delivery of certain key neurotransmitters (chemical messengers in the brain).
• The mechanism of action of citalopram as an antidepressant is presumed to be linked to potentiation of serotonergic activity in the CNS.
• Venlafaxine, an SSNRI, affects both serotonin and norepinephrine which is why it is a successful antidepressant for people who have not responded to treatment with SSRIs.
• A person taking SSRIs/SSNRIs requires careful monitoring to avoid dangerous adverse reactions and drug interactions. Some of the more common adverse reactions include anxiety, insomnia, somnolence and palpitations.
• Service users taking citalopram should be carefully monitored for orthostatic hypotension. SSRIs/SSNRIs have also been linked with an increase in suicidal ideation and aggression.
• Many of the drug interactions with SSRIs/SSNRIs are associated with their ability to competitively inhibit one of the liver enzymes that helps metabolize numerous drugs, including antipsychotics, carbamazepine, metoprolol and flecainide.
• Using SSRIs/SSNRIs with other medicines can cause a serious, potentially fatal reaction, called serotonin syndrome.
• One of the most severe adverse reactions of SSRIs/SSNRIs may occur when the patient stops taking the medication.
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