Current Psychiatry Reports

, 15:393

Psychopharmacology in Psycho-oncology

Authors

  • Rosangela Caruso
    • Institute of Psychiatry, Department of Biomedical and Specialty Surgical SciencesUniversity of Ferrara
    • Institute of Psychiatry, Department of Biomedical and Specialty Surgical SciencesUniversity of Ferrara
  • Maria Giulia Nanni
    • Institute of Psychiatry, Department of Biomedical and Specialty Surgical SciencesUniversity of Ferrara
  • Michelle Riba
    • Department of PsychiatryUniversity of Michigan
Complex Medical-Psychiatric Issues (MB Riba, Section Editor)

DOI: 10.1007/s11920-013-0393-0

Cite this article as:
Caruso, R., Grassi, L., Nanni, M.G. et al. Curr Psychiatry Rep (2013) 15: 393. doi:10.1007/s11920-013-0393-0
Part of the following topical collections:
  1. Topical Collection on Complex Medical-Psychiatric Issues

Abstract

Psychopharmacological intervention is a major clinical and research area in oncology and palliative care. Over the last 35 years, psychotropic drugs have been shown to have a number of important indications for the treatment of the most common psychiatric disorders, such as depression, anxiety, stress-related syndromes, severe adjustment disorders, sleep disorders and delirium, which combined affect at least 30-40% of patients with cancer and even a higher percentage of patients in an advanced phase of illness. The availability of new drugs, with less side-effects and safer pharmacological profiles, has been a major advance in clinical psycho-oncology. Interestingly, several drugs have also been found to be helpful for the adjuvant treatment of cancer-related symptoms, such as pain, hot flashes, pruritus, nausea and vomiting, fatigue, and cognitive impairment, making psychopharmacology an important tool for the improvement of cancer patients’ quality of life. The aim of this paper is to summarize recent relevant data concerning the use of psychotropic drugs, namely antidepressants, anxiolytics, antipsychotics, anticonvulsants and psychostimulants in patients with cancer.

Keywords

CancerPsycho-oncologyDepressionCancer-related symptomsPsychopharmacotherapyAntidepressantsAntipsychoticsSedative-hypnoticsAnticonvulsantsPsychostimulantsPsychiatry

Introduction

The need for multidisciplinary intervention and inclusion of psycho-oncology programs within the national cancer plan acts of many countries has been indicated as mandatory [1] and the need for psychosocial training of all health care professionals working in oncology is essential for good quality of cancer care [2].

With respect to this, psychopharmacology is one of the several areas of training, given the significant role of psychotropic drugs in the treatment of psychiatric disorders secondary to cancer; and the need for a comprehensive update of the new data emerging from psychopharmacological research and clinical practice in psycho-oncology [3].

In fact, a recent meta-analysis of the most significant studies in different cancer settings, including oncology, hematology and palliative care, showed that at least 25-30% of patients suffer from psychiatric disorders during their cancer care, mainly adjustment, anxiety, stress-related and depressive disorders [4••]. Further meta-analysis showed that one-third of cancer patients both in the diagnostic phase [5•] and in the acute care, when hospitalized, [6] suffered from psychiatric disorders and needed specialist treatment. In advanced phases of illness and in terminally ill patients, delirium is also extremely common [7].

For these reasons, evidence regarding the use of psychotropic drugs in oncology has accumulated over the last 35 years and represents both a pillar in the integrated treatment of psychological disorders as well as for adjuvant treatment of cancer-related symptoms (e.g., pain, hot-flashes, fatigue) [8, 9]. A recent study on 7298 cancer patients found that 15.6% of subjects met the criteria for emotional distress, versus 1.4% of healthy controls. Moreover, the volume and duration of psychotropic drugs prescriptions, mainly anxiolytics and antipsychotics, appeared significantly different between cases and controls [10•]. In another large cohort study [11] of more than 2000 breast cancer patients receiving endocrine therapy, the prescription of anxiolytics, hypnotics, sedatives and antidepressants was higher as compared to a group of age- and family physician-matched group of 8129 women without cancer. Although psychotropic drug prescribing very frequently starts soon after cancer diagnosis, it tends to increase in the terminal stage of the disease. A recent retrospective case–control study including a total of 113,887 cancer patients showed that a new prescription of a psychotropic agent was significantly lower in the first 3 months after cancer diagnosis than the 3 months before death [12]. A significant increase in the use of psychotropic drugs and a change in their profile, with a higher use of polypharmacotherapy was also found in a study exploring the change of psychotropic medications in advanced cancer patients over a seven-year period, from 2002 to 2009 [13].

On this background, this review is aimed at (i) summarizing the relevant and recent data relative to psychopharmacology in oncology, (ii) describing the most important classes of psychotropic medications, mainly antidepressants, antipsychotics, anxiolytics and anticonvulsants, and their use in the light of recent literature; and (iii) discussing recent research regarding the use of psychotropic drugs as a co-adjuvant therapy for antagonizing some of the most frequent cancer-related symptoms.

Antidepressants

Over the last several decades - mainly as a result of the availability of new classes of antidepressants (ADs) with a better tolerability and a reduced number and severity of adverse effects as compared to tricyclic ADs (TCAs) and monoamine oxidase inhibitors (MAOIs) - the use of ADs in the medically ill, including cancer patients, has taken several steps forward. These agents are mainly represented by selective serotonin reuptake inhibitors (SSRIs), selective noradrenergic reuptake inhibitors (NARIs), selective noradrenergic and serotonin reuptake inhibitors (SNRIs), selective dopamine and noradrenergic re-uptake inhibitors (NDRIs) and noradrenergic and specific serotonergic antidepressants (NaSSA). New classes of ADs, such as agomelatine, which exerts an action through melatonin receptors, are also available but their use in cancer patients deserve more research.

Depression

Depression is one of the most common disorder in cancer patients and updated research has confirmed the increase rate of ADs prescribed for cancer patients, with the intent of addressing symptoms of depression [14, 15]. A recent meta-analysis on the efficacy of psychological and pharmacologic treatments in cancer patients with elevated symptoms of depression has indicated that both approaches are effective and that treatment integration can maximize the outcome [16•].

A further systematic review and meta-analysis was recently carried out by Laoutidis and Mathiak [17•] who found that ADs, irrespective of their class (e.g., SSRIs or TCAs) are more effective than placebo in treating depressive symptoms. In the choice of antidepressant medications, however, it is essential to take into account the type of cancer, specific symptoms and other therapies and drugs in order to reduce the probability of adverse events and provide an advantageous and personalized treatment. Guidelines have been also recently developed regarding the use of ADs to manage and treat depression in the difficult setting of palliative care, where the risk of side-effects and drug interactions is high due to the patients’ severe physical conditions [18]. The most important characteristics of ADs and their rational use in cancer patients, as emerged by the most updated literature, are reported in Table 1.
Table 1

Antidepressant medications and their use in cancer patients. Modified and adapted from Grassi et al. [15]

Class

Action

Side effects

Possible disadvantages

Side effects

Possible advantages

Use in cancer patients

Trycyclic antidepressants (e.g., amitriptyline, imipramine, desipramine, clomipramine)

Inhibition of 5-HT and NA reuptake

Antimuscarinic

Antihistaminic

Anti alpha1

Constipation, dry mouth, urinary retention, memory dysfunction

Drowsiness

Postural hypotension, dizziness, reflex tachycardia

Hypotension

Action on pain

Action on sleep

Generally not used for the risky antimuscarinic side effects. If necessary, use with caution

Selective serotonin reuptake inhibitors - SSRIs (fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, escitalopram)

Inhibition of 5-HT reuptake

Sexual dysfunction (5-HT2A)

Gastrointestinal effects (nausea, vomiting, diarrhea) (5HT3)

Some more sedative (e.g. citalopram) than others

Regularly used, with the exception of fluvoxamine (high interaction with CYP). Paroxetine reported to interfere with tamoxifen

Selective noradrenaline reuptake inhibitors – NRIs (e.g., reboxetine)

Inhibition of NA reuptake

Slight antimuscarinic

Decreased blood pressure, dizziness

Possible dry mouth, urinary retention

Improved drive and cognitive functions

Not routinely used

Selective serotonin and noradrenaline reuptake inhibitors - NSRIs (e.g., venlafaxine, desvenlafaxine, duloxetine, milnacipram)

Inhibition of 5-HT and NA reuptake

Possible risk of hypertension

Action on pain

More frequently used

Selective dopamine and noradrenaline reuptake inhibitors NDRIs (e.g., bupropion)

Inhibition of dopamine and NA reuptake

Anxiety

Psychomotor activation

Increase attention and concentration

Possibly decrease fatigue

Some data on patients with fatigue or in an advance phase. Check risk of seizures

Noradrenergic and specific serotonergic antidepressants - NaSSA (e.g., mirtazapine)

Increase 5-HT and NA activity

Antihistaminic

Drowsiness

Increase appetite and weight gain

Drowsiness (helpful in case of insomnia)

More frequently used. Check possible (rare) neutropenia

Serotonin antagonist and reuptake inhibitors (trazodone, nefazodone)

Increase 5-HT activity

 

Action on sleep

Reported effects on pain

Used in the past. Nefazodone can cause liver problems

Psychostimulants (dextro-amphetamine, methylphenidate, dexmethylphenidate, modafinil)

Increase dopamine activity

Restlessness, agitation, insomnia, nightmares, psychosis, anorexia Arrhythmia, tachycardia hypertension Tolerance, dependence Seizures

Rapid effect

Action on pain

Used especially in terminally ill patients

Cancer-Related Symptoms

Clinical practice, supported by scientific evidence, has shown that ADs can be used to improve non psychiatric cancer-related symptoms, such as loss of appetite, sleep disturbances, pain, anxiety, fatigue, which remarkably interfere with quality of life.

Pain

Pain, either caused by tumor invasion or treatment (e.g., surgery, radiotherapy, neurotoxicity related to chemotherapy), is one of the most disabling conditions in cancer patients, with a high prevalence in all phases of disease, especially in the advanced phases [19]. The efficacy of ADs, particularly TCAs, as a supplementation of the primary analgesics, is well-known and recent studies confirm these data [20, 21]. In particular, the use of ADs as a co-adjuvant treatment in cancer pain has been recommended in the European Society for Medical Oncology (ESMO) Guidelines for cancer pain management [22]. Among the several classes, the newer SNRI duloxetine has proved to be effective in improving treatment of neuropathic pain in patients on chemotherapy, providing a greater symptom reduction as compared to placebo [23] and to reduce sleepiness and light-headed feeling in patients with neuropathic pain who could not use other drugs [24]. A review of 21 studies has suggested an overestimation in the efficacy of the TCAs, specifically amitriptyline, in neuropathic pain [25]. As mentioned, however, the use of TCAs has gradually decreased over time, mainly because of their anticholinergic effects, including dry mouth, which can worsen the effects of radiation in patients with head and neck cancer or of chemotherapy stomatitis, as examples; arrhythmias, in patients suffering from cardiologic pathologies; reduction of bowel peristalsis with an increase of the side-effects of opioids; risk of confusional states, especially in patients in an advanced stage of illness [16•].

Appetite and Nausea / Vomiting

ADs have also proven their efficacy in alleviating other common symptoms in patients with malignancy. The anti-histaminergic properties of mirtazapine, a NaSSA drug, have shown to be useful in counteracting nausea, chemotherapy induced anorexia/cachexia and severe weight loss [26]. More recently a phase II trial confirmed its beneficial impact on appetite, sleep disturbances, anxiety, pain and quality of life, as well as depression in cancer patients [27]. Mirtazapine is correlated with a rare risk of agranulocitosis, therefore a monitoring of white blood cell count should be performed.

Sleep Disorders

Sleep/wake cycles dysregulation is another common symptom in cancer patients that should be addressed, not only for the impact on quality of life but for a possible influence on inflammation processes and cancer progression [28]. A study on 426 cancer patients with insomnia indicated the superiority of paroxetine versus placebo in both depressed and non depressed subjects [29], although sleep disturbance rates remained elevated. A more recent observational study carried out in palliative care settings and analyzing the use of the atypical AD trazodone in cancer patients with sleep disturbances, showed an effectiveness in 50% of cases [30]. Advantages of trazodone are its non habit-forming sleep effect and anxiolytic profile. This agent, however, must be used with attention in patients with cardiovascular comorbidities (risk of orthostatic hypotension).

Hot Flashes

Selective estrogen receptor modulators (SERM), such as tamoxifen or more recent aromatase inhibitors, administered to breast cancer patients to reduce the risk of cancer recurrence, frequently cause hot flashes, with approximately two thirds of patients experiencing this symptom (60% as severe, and 40% as extremely bothersome), with unrelieved hot flashes related to negative affect, fatigue, sleep difficulties, and overall poor quality of life [31]. ADs, especially SSRIs and SNRIs, have been shown to be effective in treating hot flashes. The first data accumulated regarded the benefit of fluoxetine, followed by paroxetine and sertraline. Likewise, randomized controlled trials using the SNRI venlafaxine showed benefit in ameliorating hot flashes, with data showing at least a 50% decrease in hot flashes, significant improvement in fatigue, sleep quality, and quality of life [32].

However, one of the problems that emerged in the last 10 years regarding the use of ADs in breast cancer patients receiving SERM, is the risk of interacting with tamoxifen metabolism and perhaps reducing its efficacy. In fact, to be clinically active tamoxifen is converted to 4-hydroxy-tamoxifen (endoxifen) and other active metabolites by cytochrome P450 (CYP) enzymes. More than 80 different major alleles of CYP2D6 gene have been identified, many of which confer decreased or absent CYP2D6 activity. Patients can be divided into poor, intermediate, extensive, and ultrarapid metabolizers on the basis of their genotype. The use of psychotropic drugs inhibiting CYP2D6 may determine a decrease in the plasma concentration of endoxifen, suggesting that CYP2D6 genotype and drug interactions should be considered in all women treated with tamoxifen [32]. Data have accumulated showing that paroxetine, fluoxetine, venlafaxine and bupropion, have significant CYP2D6-inhibiting properties and thus, at the current time, should be avoided in cancer patients treated with tamoxifen [33, 34•]. A recent review of 26 randomized controlled trials [35] aiming at providing up-to-date evidence-based recommendations on non-hormonal pharmacological interventions for the management of hot flashes in cancer patients, showed that venlafaxine, citalopram, clonidine, gabapentin and pregabalin can be considered effective and safer than paroxetine and fluoxetine in breast cancer patients on tamoxifen. However, although recommendations have been dispensed for the latest years, between 2005 and 2010 paroxetine was still one of the most prescribed antidepressants in women on tamoxifen [36].

Fatigue

Fatigue is also a common symptom affecting up to 91% of cancer patients, depending on the specific populations studied and the methods of assessment [37••]. The antidepressant NDRI bupropion, which is also effective in smoking cessation, may be of help in cancer-related fatigue [38], maybe for its dopaminergic activity.

The use of the newest ADs among patients with cancer should consider the possible adverse effects of these drugs that, in spite of the safe profile, may induce discontinuation syndrome (more often observed with venlafaxine and paroxetine, for their shorter half-life), the risk of bleeding, seizures, cardiovascular disorders, hyponatremia, as well as serotoninergic syndrome [39].

Antipsychotics

Antipsychotics (APs), especially conventional APs (e.g., phenothiazines, butyrophenones) have been used for many years in the management of preexisting psychiatric conditions, as well as in the treatment of some medical symptoms and chemotherapy side-effects in patients with cancer [40]. Advances in psychopharmacology of APs, in particular the development of atypical APs (e.g., aripiprazole, olanzapine, quetiapine, risperidone, zyprasidone) have improved the treatment of psychotic disorders and other psychiatric and non-psychiatric symptoms affecting cancer patients.

Delirium

Both typical and atypical APs play an important role in the symptomatic treatment of delirium. A recent systematic review evaluated the effectiveness of different drug therapies to treat delirium in terminally ill patients [41], showing equal efficacy between phenothiazines (i.e., chlorpromazine) and butyrophenones (i.e., haloperidol) in the short term, while at subsequent follow-up cognitive status was reduced in patients treated with chlorpromazine. No improvement was observed in patients treated with lorazepam, who instead developed increasing confusion, leading to drug discontinuation. A further recent review confirms the role of haloperidol as a first line drug in cancer patients, underlining the need for short-term, low-dose use of APs and close monitoring for possible adverse effects, especially in older patients with multiple medical comorbidities [42••].

Recent reports indicated the clinical efficacy of risperidone (mean dosage: 1.4 ± 1.3 mg/day) for the treatment of delirium in cancer patients, with outcomes showing that 48% of patients responded and 38% achieved remission, indicating that risperidone is effective in treating delirium, independent of the severity of the underlying illness [43]. In a pilot study on the safety and tolerability of subcutaneous olanzapine it has been shown that the drug is well tolerated, but further research is needed to evaluate its efficacy [44].

While there is agreement on the use of APs to treat delirium, data are quite controversial about dosages. A study exploring APs prescription patterns for 100 patients treated for delirium with haloperidol (94%), olanzapine (8%) and chlorpromazine (5%), documented that the median haloperidol equivalent daily dose (HEDD) was 3.2 mg, indicating a decrease of HEDD as compared with previous data [45]. Another study interestingly evidenced how HEDD was influenced more by health care professional distress and preoccupation than by actual delirium symptoms frequency [46]. These findings underline the need for further prospective trials to better identify optimal doses of APs in these contexts, considering the complexity of clinical conditions (e.g., polypharmacotherapy, organ failures) among patients with advanced disease.

Cancer-Related Symptoms

As for ADs, APs have also been used in oncology to alleviate cancer-related symptoms, including nausea and vomiting and pain.

Nausea and Vomiting

The efficacy of APs in cancer settings has also been demonstrated for the treatment of nausea and vomiting [40]. These are frequent and disabling symptoms in cancer which carry a multifactorial etiology and can be responsible for dehydration, malnutrition, reduced performance status and poor quality of life [47]. Several drug classes are used with the purpose of alleviating nausea and vomiting in cancer patients. Studies report that metoclopramide alone or in combination with a phenothiazine is considered the first-line treatment, followed by haloperidol as an alternative antiemetic. Although the use of haloperidol in cancer patients has been supported by scientific evidence, a recent review outlined the insufficiency of direct evidence and the need to further analyze its efficacy [48].

For patients who do not respond to first-line antiemetics, olanzapine has been diffusely indicated as a second-line therapy [49]. Although sharing with the antiemetic ondansetrone a similar affinity to 3-HT receptors, it has a longer half life, shows antianxiety effects and improves sleep quality. As a single agent, olanzapine can be advantageous over antiemetic combinations by improving adherence, reducing the risks of drug interactions and allowing several routes of administration [50].

Psychosis

Cancer diagnosis and treatment may predictably worsen psychotic symptoms in patients with previous severe mental disorders. Moreover, some medications frequently prescribed in oncology practice can exacerbate a pre-existing psychotic condition, thus further impairing a generally poor quality of life [51]. In addition, cancer patients may present neurologic and psychiatric symptoms with altered mental status, seizures, paraneoplastic encephalitis, that in some cases may be the presenting symptom of malignancy [52]. Independently of the nature of psychotic symptoms, APs remain the therapy of choice for delusions, hallucinations and thought disorganization. Nonetheless, treating the medical etiology, when possible, is of primary importance.

Anxiety, Depression and Sleep Disorders

Antipsychotic monotherapy or, more frequently, in augmentation regimens, can be useful in the treatment of non psychotic conditions, such as anxiety, sleep disturbances and depression in cancer patients.

Recent literature suggests that medical conditions contraindicating the use of benzodiazepines, such as delirium, dementia or respiratory depression, may be managed successfully by using atypical antipsychotics with a sedative profile, including quetiapine and olanzapine [53].

In resistant depression, augmentation with atypical APs, especially quetiapine, aripiprazole, olanzapine, and risperidone, is quite common in clinical practice and has shown higher response and remission rates compared to antidepressant monotherapy, even though it is associated with more drop-outs due to adverse events [54]. Such a strategy may be useful in psycho-oncology as well, but it requires a careful and constant monitoring.

As for the other psychotropics, an accurate evaluation of medical conditions is fundamental in order to select the most appropriate agents and reduce the risk of adverse reactions and interactions. The most common side-effects of APs include extrapyramidal reactions, orthostatic hypotension, cardiologic effects (e.g., QTc interval prolongation) and severe arrhythmias, endocrine and metabolic syndromes (i.e., hyperprolactinemia, dyslipidemia, weight gain, insulin resistance); excessive sedation, reduction of epileptic threshold, hematologic disorders, and antimuscarinic effects (with increased risk of delirium, constipation, dry mouth, and urinary retention). Extrapyramidal reactions are more frequently caused by high potency neuroleptics and high doses of risperidone. The association of antiemetics and antipsychotics can in some cases generate akathisia. QT interval prolongation is linked with rare but life-threatening arrhythmias and it is more often correlated with intravenous haloperidol, zyprasidone and quetiapine [55].

Olanzapine, quetiapine and risperidone are associated more than other antipsychotics to endocrine and metabolic disorders [56], while chlorpromazine, olanzapine and quetiapine can reduce the epileptic threshold [57] and should be avoided or strictly monitored in patients with CNS diseases as well as those on corticosteroids. Antipsychotic-related hematologic disorders (neutropenia, aplastic anemia, thrombocytopenia and rarely agranulocytosis), observed with clozapine and some atypical antipsychotics [58] must be taken into account especially for myelosuppressed patients. The association with other anticholinergics can exacerbate antimuscarinic effects. Drug-drug interaction are in many cases due to the cytocrome P450 system and can occur with the association of dexamethasone, antibiotics, anticonvulsants and antidepressants [59]. Also, there has been some study and concern about the use of antipsychotic drugs in their administration to patients with breast cancer due to the elevation of serum levels of prolactin (PRL) [60].

Anxiolytics and Hypnotics

Benzodiazepines

Benzodiazepines (BDZ) represent for a long time a useful aid in cancer care for the treatment of symptomatic anxiety and insomnia [61]. Nevertheless, due to the potentiality of generating tolerance, dependence and abuse, their use should be limited to acute conditions and accompanied by a careful anamnesis of the etiology of presented symptoms; antidepressants – as seen before – are the pharmacologic treatment of choice for a long-term management of anxiety disorders. In cancer patients, BDZ are contraindicated in respiratory depression or bradycardia. In combination with antiemetics and behavioral techniques, BDZ can be effective for chemotherapy-related anticipatory nausea [62]. Certain BDZ side-effects, namely sedation, dizziness and incoordination can contribute to sense of fatigue and weakness. In some cases, BDZ may also complicate disorientation and impaired memory or even generate paradoxical effects in patients with central nervous system damage [63]. Midazolam, a benzodiazepine often used as an intravenous anesthetic in the treatment of patients with cancer, has been correlated in a study with an increased risk of coma, while delirium was unrelated to this agent [64].

In the treatment of sleep disorders in cancer settings, non-BDZ hypnotic, such as zolpidem, zopiclone, eszopiclone and zalepon are commonly used in clinical practice, both alone or in combination with other psychotroic drugs [65, 66]. More research is however necessary, since no evidence from randomized controlled trials was identified. Therefore it is difficult to draw any conclusions regarding the use of BDZ and non-BDZ in cancer settings, especially in palliative care [67].

Anticonvulsants

Anticonvulsants (AEDs) along with atypical APs and lithium are traditionally used to treat bipolar and bipolar spectrum disorders. Lithium, however, is rarely used in the medically ill, due to its potential interactions and toxicity [68], while AEDs are generally safer and better tolerated by medically ill patients.

In cancer care, AEDs are frequently used alone or in combination in the management of neuropathic pain. Gabapentin and pregabalin are particularly indicated for this purpose, because of their very minimal pharmacological interactions and their anxiolytic profile [19, 69•].

Valproate and carbamazepine can be helpful in manic-spectrum syndromes secondary to steroids or brain tumors [70]. Attention should be paid to the interaction with the metabolism of other drugs via the cytochrome P450 enzyme system and to the side-effects, including myelosuppression, ataxia, gastrointestinal disturbance, weight gain, and hepatotoxicity.

AEDs are also used in seizure control in brain tumor-related epilepsy. In patients with brain tumor, seizures are the onset symptom in 20-40% of patients, while a further 20-45% will present them during the course of the disease. In these patients, new generation drugs such as gabapentin, lacosamide, levetiracetam, oxcarbazepine, pregabalin, topiramate, zonisamide are generally preferred because of fewer interactions and side-effects [71]. Among the most recent agents, lacosamide has demonstrated promising results [72].

Psychostimulants

Psychostimulants (e.g., methylphenidate, pemoline, d-amphetamine), although not frequently recommended in psychiatry (apart from attention-deficit hyperactivity disorders in children and adoloscents), have been used in the treatment of depression in medically ill patients, especially the terminally ill patients and cancer patients, for a long time [73, 74]. Their rapid onset of action (unlike ADs that have a latency of 3–4 weeks) and their effect on other symptoms of depression in the terminally ill, including attention and concentration problems, make this class of drugs interesting, although randomized clinical trials are lacking [73].

Besides depression, the treatment of cancer-related fatigue has ben the object of research, with data showing the possible role of psychostimulants, including the more recent modafanil, a wakefulness-promoting agent. A recent review [75•] indicated that for the relief of asthenia secondary to chemotherapy, methylphenidate and modafinil were no more effective than placebo, although findings suggest that these psychostimulants may provide some benefit in patients who are suffering more severe asthenia or who are at advanced stages of illness. Other reviews and metanalysis [76•, 77•] underlined the preliminary evidence for the use of psychostimulants to treat cancer-related fatigue, with further confirmation needed before firm recommendations on their usage and safety can be made. The same recommendation of more studies needed, regards the possible use of psychostimulants, particularly modafanil, as cognitive enhancers among cancer survivors suffering from cognitive impairment due to therapy [78, 79].

Conclusions

In this review, we have tried to present the updated information regarding psychotropic medications in cancer settings and their most common use in clinical settings (Table 2).
Table 2

Most common disorders in cancer patients that can be treated by using psychotropic drugs. Modified and adapted from Thekdi et al. [3]

Psychiatric disorders

 • Major Depressive Disorder (MDD): ADs in general (according to the several guidelines available): attention to drugs side-effects, drug interaction and medical conditions.

 • Post-Traumatic Stress Disorder (PTSD): SSRIs (sertraline,paroxetine are FDA-approved for the treatment of PTSD).

 • Panic Disorder: SSRIs (fluoxetine, paroxetine, sertraline are FDA-approved) and SNRIs (venlafaxine).

 • General Anxiety Disorder: SSRIs (fluoxetine, paroxetine, escitalopram, sertraline), SNRIs (venlafaxine, duloxetine); pregabalin.

 • Delirium: Typical antipsychotics (haloperidol FDA-approved); atypical antipsychotics (risperidone, olanzapine, quetiapine); BDZ in alcohol-withdrawal delirium

Cancer-related symptoms or disorders

 • Chronic and neuropathic pain: TCAs (amitriptyline), SNRIs (duloxetine, venlafaxine) in combination with other pain medications; anticonvulsants (valproate, gabapentin, pregabalin)

 • Hot flashes (in breast cancer survivors): SSRIs (citalopram); SNRIs (venlafaxine, and desvenlafaxine is being studied) (NB: caution regarding specific medications for women taking tamoxifen).

 • Anorexia and cachexia: TCAs (amitriptyline, imipramine), NaSSA (mirtazapine)

 • Cancer-related fatigue: Psychostimulants (methylphenidate, modafinil), NDRIs (bupropion)

 • Sleep disturbances: BDZ (use with caution) and non-BDZ agents (zolpidem, zopiclone, eszopiclone), SSRIs (citalopram), NaSSA (mirtazapine), trazodone, SNRIs (venlafaxine, duloxetine)

Since psychiatric disorders are common in patients with cancer and negatively influence their quality of life, knowing and understanding the use of the most important drugs is important for both mental health and cancer professionals. In fact, cancer patients usually present a complex symptomatology which are treated by using many different therapies, including polypharmacotherapy and psychotherapy, as well as other treatments such as electroconvulsive therapy, behavioral therapies, complementary therapies, and so on. Thus, a proper and rational administration of psychotropic drugs requires a multidisciplinary strategy and a personalized approach.

In a world which is becoming more and more cross-cultural, social and ethnic variables should also be taken into account when selecting treatment, since cultural values may further influence the onset and the course of psychiatric disorders, as well as the patients’ adherence and response to treatment. For instance, it has been indicated that lower socio-economic status, immigrant, and premorbid chronic medical conditions are predictors of a higher use of psychotropics in cancer populations [12].

As for drug side-effects and interactions, differential frequency of cytochrome P450 enzyme allelic variants have been shown between Asians and Africans and European Caucasians, the latter less commonly having hypo-functioning or non-functional 2D6 alleles [80]. This impacts on the metabolism of numerous medications reported above, and poses the need for the physician to adjust doses and be aware of the potential drug-drug interactions. In this view, it is of tremendous importance that health care providers practicing in oncology settings become familiar with the most used classes of psychotropic drugs, indications and interaction profiles related to their use.

Another major issue in psycho-oncology settings is represented by the increasing use of complementary medicine among cancer patients [81]. While many natural remedies may have an important role in alleviating physical and mental symptoms of cancer, they may also present pharmacokinetic and pharmacodynamic mechanisms that interact with conventional drugs, increasing the potential of adverse events. An investigation of the use of homeopathic and herbal remedies is therefore mandatory when prescribing psychotropic drugs in cancer care.

For these purposes, continual medical education, guidelines and the development of databases which simplify the search of clinically relevant interactions between anticancer and psychotropic drugs, have been indicated as valuable means to improve scientific knowledge and pharmacological care of cancer patients [3].

In summary, a clear understanding of the prevalence of common mental disorders and their treatment in cancer patients is particularly important given the evidence that untreated or undertreated psychiatric comorbidity is correlated with worsened disability, poorer quality of life and lower adherence to cancer treatment. Understandably, however, this requires an approach concerned not only with biological therapies (e.g., pharmacotherapy, surgery, radiation) but also with integrated psychosocial-focused interventions for the individual throughout all phases of the illness, in order to reach a more integrated and holistic care of cancer.

Compliance with Ethics Guidelines

Conflict of Interest

Rosangela Caruso declares that she has no conflict of interest.

Luigi Grassi has received royalties from Oxford University Press.

Maria Giulia Nanni declares that she has no conflict of interest.

Michelle Riba declares that she has no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Copyright information

© Springer Science+Business Media New York 2013