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1. Wefel JS, Saleeba AK, Buzdar AU et al. Acute and late onset cognitive dysfunction associated with chemotherapy in women with breast cancer. Cancer 2010; 116(14): 3348–562. Muni F, Burrows J, Yarker J et al. Women’s perceptions of chemotherapy-induced cognitive side effects on work ability. J Clin Nurs 2010; 19(9–10): 1362–703. Debess J, Riis JØ, Engebjerg MC et al. Cognitive function after adjuvant treatment for early breast cancer: a population-based longitudinal study. Breast Cancer Res Treat 2010; 121(1): 91–1004. Yamada TH, Denburg NL, Beglinger LJ et al. Neuropsychological outcomes of older breast cancer survivors: cognitive features ten or more years after chemotherapy. J Neuropsychiatry Clin Neurosci 2010; 22(1): 48–545. Schilder CM, Seynaeve C, Beex LV et al. Effects of tamoxifen and exemestane on cognitive functioning of postmenopausal patients with breast cancer: results from the neuropsychological side study of the tamoxifen and exemestane adjuvant trial. J Clin Oncol 2010; 28(8): 1294–3006. Tager FA, McKinley PS, Schnabel FR et al. The cognitive effects of chemotherapy in post-menopausal breast cancer patients: a controlled longitudinal study. Breast Cancer Res Treat 2010; 123(1): 25–347. Vardy J and Dhillon H. The fog hasn’t lifted on “chemobrain” yet: ongoing uncertainty regarding the effects of chemotherapy and breast cancer on cognition. Breast Cancer Res Treat 2010; 123(1): 35–78. Boykoff N, Moieni M, and Subramanian, SK. Confronting chemobrain: an in-depth look at survivors’ reports of impact on work, social networks, and health care response. J Cancer Surviv 2009; 3(4): 223–329. Vearncombe KJ, Rolfe M, Wright M et al. Predictors of cognitive decline after chemotherapy in breast cancer patients. J Int Neuropsychol Soc 2009; 15(6): 951–6210. Reid-Arndt SA, Hsieh C, and Perry MC. Neuropsychological functioning and quality of life during the first year after completing chemotherapy for breast cancer. Psychooncology 2010; 19(5): 535–4411. Kohli S, Fisher SG, Tra Y et al. The effect of modafinil on cognitive function in breast cancer survivors. Cancer 2009; 115912): 2605–1612. Jim HS, Donovan KA, Small BJ et al. Cognitive functioning in breast cancer survivors: a controlled comparison. Cancer 2009; 115(8): 1776–8313. Weis J, Poppelreuter M, and Bartsch HH. Cognitive deficits as long-term side-effects of adjuvant therapy in breast cancer patients: ‘subjective’ complaints and ‘objective’ neuropsychological test results. Psychooncology 2009; 18(7): 775–8214. Castellon S and Ganz PA. Neuropsychological studies in breast cancer: in search of chemobrain. Breast Cancer Res Treat 2009; 116(1): 125–715. Mehlsen M, Pedersen AD, Jensen AB et al. No indications of cognitive side-effects in a prospective study of breast cancer patients receiving adjuvant chemotherapy. Psychooncology 2009; 18(3): 248–5716. Quesnel C, Savard J, and Ivers H. Cognitive impairments associated with breast cancer treatments: results from a longitudinal study. Breast Cancer Res Treat 2009; 116(1): 113–2317. Stahl SM, Cognition, in Stahl’s Essential Psychopharmacology, 3rd edition, Cambridge University Press, New York, 2008, chapter 19, pp 943–101218. Stahl SM, Modafinil, in Stahl’s Essential Psychopharmacology The Prescriber’s Guide, 3rd edition, Cambridge University Press, New York, 2009, pp 359–6319. Stahl SM, Donepezil, in Stahl’s Essential Psychopharmacology The Prescriber’s Guide, 3rd edition, Cambridge University Press, New York, 2009, pp 145–920. Stahl SM, Bupropion, in Stahl’s Essential Psychopharmacology The Prescriber’s Guide, 3rd edition, Cambridge University Press, New York, 2009, pp 57–6221. Stahl SM, Atomoxetine, in Stahl’s Essential Psychopharmacology The Prescriber’s Guide, 3rd edition, Cambridge University Press, New York, 2009, pp 51–522. Stahl SM, Methylphenidate, in Stahl’s Essential Psychopharmacology The Prescriber’s Guide, 3rd edition, Cambridge University Press, New York, 2009, pp 329–35

Patient FileLightning RoundThe Case: The woman who has always been out of control

The Question: How do you treat chaos?

The Dilemma: What can you expect from an antipsychotic in a woman with many problems and diagnoses?

Pretest Self Assessment Question(answer at the end of the case) How do you approach multiple comorbidities in a chronically mentally ill patient who has essentially never been in good symptomatic control?

A. Empiric trials of antipsychotics

B. Empiric trials of mood stabilizing anticonvulsants

C. The correct combination of medications generally can control most symptoms in most patients at most times

D. Realize that full remission may not be the goal of treatment for some severe longstanding cases, but the goal may be to attain the best level of functioning that the patient has experienced in recent years

E. Aggressive polypharmacy has its limits

Patient Intake 30-year-old woman diagnosed with long-standing schizoaffective disorder, bipolar type, polysubstance abuse in remission in a controlled environment and with premorbid childhood onset PTSD, borderline intellectual functions, and antisocial personality disorder with borderline features

Has carried the diagnosis of PTSD related to childhood sexual and physical abuse by her father

Juvenile and adult criminal activity and poor school performance, with cognitive testing showing cognitive and memory abilities in the borderline range

Difficulty managing anger since age 13, longstanding impulsiveness since age 13 with psychotic illness since age 16 associated with irritable and depressed moods, auditory hallucinations (some in her father’s voice) command hallucinations to harm herself, ideas of reference and persecutory ideation

Numerous psychiatric hospitalizations, self mutilatory behavior including cutting and swallowing behaviors (e.g., keys, other objects)

Convicted of arson and while imprisoned assaulted a prison guard but found not to be criminally responsible by reason of insanity and transferred to a forensic facility

Psychiatric History Intermittent violent and self injurious behavior associated with continuing psychotic symptoms, mood lability, and impulsiveness

Current psychotropic medications:– Haloperidol (Haldol) 10 mg at noon and 5 mg at night– Ziprasidone (Geodon) 80 mg twice a day– Lithium 600 mg at noon and 900 mg at night– Modafinil (Provigil) 200 mg at noon– Duloxetine (Cymbalta) 60 mg at noon– Propranolol (Inderal) 15 mg three times a day– Phenytoin (Dilantin) 400 mg twice a day– Levothyroxine 225 µg per day– Zolpidem (Ambien) 10 mg at night– Quetiapine (Seroquel) 200 mg prn

Of the following choices, what would you do?

Increase the dose of one or more antipsychotics

Switch one of the antipsychotics to another one

Increase the dose of duloxetine

Trials of other anticonvulsants such as topiramate (Topamax), lamotrigine (Lamictal), valproate (Depakote)

Emphasize nonpharmacological approaches

Case Outcome At first, haloperidol was increased to 20 mg a day, and olanzapine was added at 20 mg, increasing to 40 mg a day, while discontinuing ziprasidone with no notable changes

Topiramate augmentation was tried, and duloxetine was increased to 60 mg twice a day

Then quetiapine 800 mg a day was substituted for olanzapine

In the interim, the patient received more nursing attention, more structured time, and occasional intramuscular administration of addition haloperidol or olanzapine or lorazepam (Ativan)

Although the worst excesses of her behaviors were blunted, the patient continues to have uncontrolled symptoms at times

Case Debrief It is important not to expect too much of medication treatment in general and antipsychotic treatment in particular

Thus, although some patients respond to even higher doses of quetiapine (>800 mg/day) this is not deemed to be likely to be helpful

Antisocial personality disorder, impulsivity related to borderline intellectual functioning, and long-standing symptoms of PTSD are among the many symptoms that often do not respond to psychopharmacological interventions and have no approved treatments and few well studied treatments

It is possible that the patient has arrived at the best functioning she can have at the present time

Posttest Self Assessment Question: Answer How do you approach multiple comorbidities in a chronically mentally ill patient who has essentially never been in good symptomatic control?

A. Empiric trials of antipsychotics

– Definitely justified

B. Empiric trials of mood stabilizing anticonvulsants

– Also justified

C. The correct combination of medications generally can control most symptoms in most patients at most times

– This is unfortunately not true for severe cases, and especially those who end up institutionalized

D. Realize that full remission may not be the goal of treatment for some severe longstanding cases, but the goal may be to attain the best level of functioning that the patient has experienced in recent years

– Knowing how to lower expectations while remaining in a therapeutic mind set and improving the situation is an important skill in managing severe cases

E. Aggressive polypharmacy has its limits

– Although clever psychopharmacology and “thinking outside the box” to fashion creative solutions for complex patients is part of the art of psychopharmacology, it is also useful to respect the limits of this approach

Answer: A,B, D and E