Antidepressants apathy

Injury to certain areas within the brain s frontal lobes may produce a syndrome that resembles depression but without depressed mood or a sad affect. Instead, this apathetic syndrome is marked by a lack of motivation, little emotional response, profound psychomotor slowing, and disengagement from social interaction. Antidepressants, stimulants, and medicines that specihcally boost dopamine activity have been tried when treating apathy after TBI (see Table 12.1). 

Antidepressants. As a rule, medicines that increase dopaminergic activity in the brain seem to work best when treating post-TBI apathy. Most antidepressants, however, work primarily by increasing serotonergic and/or noradrenergic activity. 

Stimulants such as amphetamine and methylphenidate have been used to treat depression for many years. Stimulants should not be used alone, except perhaps in geriatric patients with prominent apathy, medically ill patients with depression, or patients with poststroke depression (Lingam et al. 1988). However, psychostimulants are useful for augmentation of antidepressant therapy in refractory depression, and they are generally safe, even for most patients with cardiac disorders. The nonamphetamine stimulant modafmil was found to be helpful in a recent placebo-controlled study involving 311 patients with partial response to SSRIs (Fava et al. 2005). 

There also has been great interest in the use of stimulants to treat depressive symptoms. Small case series suggest the potential usefulness of adding stimulants to antidepressant therapy in treatment-resistant depression (Masand et al. 1998 Stoll et al. 1996). Stimulants also have been used in the treatment of depressive symptoms in medically ill elderly patients (see reviews by Challman and Lipsky 2000 and Masand and Tesar 1996). Short-term use of stimulants may rapidly improve symptoms of apathy and social withdrawal in these patients. 

There is a clinical impression that psychostimulants may be helpful in HIV- or AIDS-related affective syndromes (487, 488). Thus, methylphenidate 10 to 20 mg per day (up to 40 mg per day) or dextroamphetamine 5 to 15 mg per day (up to 60 mg per day) has been helpful in patients with mild depression who also show symptoms of social withdrawal, fatigue, and apathy, as well as mild cognitive impairment. At times, the combination of low-dose antidepressant and psychostimulant may be more effective and less likely to induce adverse CNS effects. 

Methylphenidate also has been used to treat other medical conditions. For example, it has been used as a short-term treatment for depression in the medically ill, as an adjunct to conventional antidepressants for patients with major depressive disorder, and in combination with opiates for pain control. Methylphenidate has been prescribed to reduce apathy in patients with dementia or other brain diseases (28,34,35). 

This is defined as any condition which mimics dementia. The commonest psychiatric disorder which mimics dementia is depression in which the retardation can be confused with the apathy of dementia. The guiding principle is careful clinical assessment and, if in doubt, a trial of an appropriate antidepressant. 

In their review of 12 reported cases, Barnhart et al. (2004) found three cases associated with fluvoxamine, seven with fluoxetine, and two with paroxetine. The apathy states improved or resolved with dose reduction or discontinuation. The authors believed that the syndrome frequently goes undetected despite its significant clinical impact. Opbroek et al. (2002) reported that 80% of patients with SSRI-induced sexual dysfunction reported suffering from treatment-emergent emotional blunting. This is consistent with my clinical observations that so-called sexual dysfunction in patients receiving antidepressants often involves a more generalized loss of interest in both sex and loved ones. 

The initial euphoria associated with mild cases of drug-induced mania often offer relief and hope, however unrealistic, to the patients who experience it. If the euphoria does not progress to full-blown mania, it is likely to wear off, and then apathy becomes more dominant over time. This often leads patients to ask for one antidepressant after another in the hope of recapturing that brief high. ... 

In my clinical practice, I have occasionally seen otherwise normal patients who were put into states of apathy or lethargy by very small doses of tricyclic antidepressants (e.g., 10 mg to 25 mg of amitriptyline) given to them for nonpsychiatric purposes, especially to treat headache or diarrhea. Depressed patients are frequendy made more depressed by these drugs without the spellbound patients or their doctors perceiving that the drug is causing the worsened condition. 

In my experience, any of the antidepressants can produce a variety of unexpected and sometimes severe emotional reactions, including apathy, lethargy, and depression, or euphoria, paranoia, and mania. Frequently, these adverse effects are mentioned as possibilities on the FDA-approved label. 

In summary, there is incontrovertible evidence that antidepressants cause suicidality, irritability, violence, and mania as well as a wide range of other psychiatric adverse drug reactions often related to overstimulation, such as insomnia, anxiety, agitation, emotional instability, and akathisia. They can also cause apathy and emotional indifference. There is also strong evidence that they cause lasting abnormalities in brain function and even brain anatomy, including abnormal brain cell proliferation, death of brain cells, and shrinkage of brain tissue. 

Can be added to SSRIs to reverse SSRI-induced sexual dystunction, SSRI-induced apathy (use combinations of antidepressants with caution as this may... 

Antidepressants if concomitant depression, apathy, or lack of interest... 

If treatment A/ith antidepressants fails to improve apathy and depressed mood in the elderly, it is possible that this represents early Alzheimer disease and a cholinesterase inhibitor like galantamine may be helpful... 

It is indicated in the treatment of depressive episodes associated with bipolar disorder. A combination of an antipsychotic drug and an antidepressant may be useful in some cases, especially in depressed psychotic patients, or in cases of agitated major depression with psychotic features. The first combination antipsychotic/antidepressant (olanza-pine/fluoxetine Symbyax) was recently FDA approved in the United States for treatment of depressive episodes associated with bipolar disorder. However, antidepressants and stimulants are unlikely to reduce apathy and withdrawal in schizophrenia, and they may induce clinical worsening in some cases. Adjunctive addition of lithium or an antimanic anticonvulsant, such as carbamazepine, may add benefit in some psychotic patients with prominent affective, aggressive, or resistant symptoms. 

Additional studies on oxypertine (XIX) indicate that the major advantage of this compound is its mood elevating and stimulant properties in schizophrenics where apathy is a major problem.In a double blind study with chlorpromazine oxypertine was judged to be of value in the treatment of chronic schizophrenia, In two clinical studies, molindone (XX) was shown to be equal to trifluoperazine as an antipsychotic but antidepressant properties were not noted at the dosage used. "... 

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