The severity and complications of depression in patients with comorbid panic disorder tend to be greater than with either depression or panic alone. Very low doses of SSRI or tricyclic treatment may be needed to prevent exacerbation of the panic. Reports of starting doses of fluoxetine as low as 1 or 2 mg per day have appeared.¹ Addition of clonazepam or alprazolam appears to be the first option if the antidepressant alone does not control the panic. Valproic acid has been reported to help some treatment-resistant cases.² An older literature finds MAOI's useful for panic disorder and may be considered if SSRI's are first removed (at least five week wait required for fluoxetine before an MAOI can be started.) Nefazodone³ and venlafaxine(4) are important options. Mirtazapine is plausible as an option but so far there is little experience reported in the literature.
The problem of comorbid panic disorder (and other anxiety disorders) and substance abuse/dependence, accompanied by depression, is seen quite often. We have developed an algorithm for managing the pharmacotherapy of these patients which will be computerized. It is available now in printed format.(5)
Recommendation #36
¹Roy-Byrne PP, Wingerson D. Pharmacotherapy of anxiety disorders. In: Tasman A, Riba MB, eds. APA Press Review of Psychiatry, Vol. 11. Washington, DC: APA Press 1992:260-284.
²Woodman CL, Noyes R, Jr. Panic disorder: treatment with valproate. J Clin Psychiatry 1994;55:134-136.
³Brawman-Mintzer O, Lydiard RB. Psychopharmacology of anxiety disorder: treatment resistance. Psychiatric Clin N Am Ann of Drug Ther 1996;3:66-67. DeMartinis NA, Schweizer E, Rickels K. An open-label trial of nefazodone in high comorbidity panic disorder. J Clin Psychiatry 1996;57:245-248.
(4)Pollack MH, Otto MW, Worthington JJ, et al. Venlafaxine for panic disorder: results from a double-blind, placebo-controlled study. Psychopharmacology Bull 1996;32:667-670.
(5)Osser DN, Bayog R, Renner JA JR. Algorithms for the pharmacotherapy of anxiety disorders in patients with chemical abuse and dependence. Psychiatric Annals 1999;29(5):285-300.
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In treating OCD, dosage of SSRI medications generally need to be higher and duration of SSRI trials in OCD usually need to be longer than in treating depression. Thus, for example, 60-80 mg per day of fluoxetine for 10 weeks may be needed. Improvement in depression does not correlate with improvement in OCD symptoms. Fluvoxamine (Luvox) is an SSRI marketed in the United States for OCD. However, we are aware of no reason to think it has superior efficacy for OCD to the other SSRI's available, nor is there a strong impression that failure of one SSRI for OCD is frequently followed by success with another SSRI. On the other hand, a meta-analysis¹ and the opinion of many clinicians experienced in treating OCD indicate that clomipramine may be the most powerful single drug for OCD (although not the first-line medication): 250 mg per day is the typical dose.
Augmentation strategies involving buspirone, clonazepam, and lithium are occasionally helpful, and clomipramine has been added to SSRI's with good results but caution is advised because of many drug interaction issues and side effects reported.² MAOI's seem to have little extra to offer but may help in treatment-resistant cases with symmetry obsessions.³ If psychotic features are present, or if the patient has a schizotypal personality along with OCD, addition of a neuroleptic may be necessary. Risperidone has been reported to both improve and worsen OCD symptoms, so the final determination of its relative value compared to standard neuroleptics in this situation is still unfolding. Clozapine has been reported to sometimes exacerbate OCD symptoms in chronic schizophrenia. However, there are reports of its successful use in intractable cases of OCD in persons without a primary psychotic disorder.
An excellent treatment algorithm for OCD is Expert Consensus guideline, which elaborates on the above issues and much more.(4)
Recommendation #35
¹Abramowitz JS. Effectiveness of psychological and pharmacological treatment of obsessive-compulsive disorder. J of Consulting and Clinical Psychology 1997;65:44-52
²Oesterheld JR, Osser DN. Drug interactions in augmentation strategies for pharmacotherapy of OCD. Journal of Psychiatry and Behavioral Health 1999;6(5): in press.
³Jenike MA, Baer L, Minichiello WE, et al. Placebo-controlled trial of fluoxetine and phenelzine for OCD. Am J Psychiatry 1997;154:1261-1264.
(4)March JS, Frances A, Carpenter D, Kahn DA, Eds. Treatment of OCD: The expert consensus guideline series. J Clin Psychiatry 1997[suppl 4];58:1-70.
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Depression may enhance the perception of pain. Adequate antidepressant therapy tends to be effective in such cases. When the primary problem is pain, and depression is secondary, psychopharmacologic treatment is usually initiated by non-psychiatric physicians. Psychiatrists tend not to be aware of the large relevant literature. A meta-analysis of 175 studies from this literature concluded that the most effective medication is clomipramine, which was superior to other antidepressants in four of eight comparisons, and equal in the other four. The next best was amitriptyline, which was superior to the comparison antidepressant in 3 studies, equal in 3 and inferior in 4 (including the two direct comparisons with clomipramine).¹ SSRI's seem significantly inferior to tertiary amine tricyclics, although one study with paroxetine showed that it was fairly effective compared to placebo and about equal to imipramine, but was better tolerated.²
A more recent review of the pain management efficacy of newer antidepressants concluded that the evidence did not permit conclusion that the newer drugs are as consistently effective as the tricyclics and that "TCAs should probably remain as first-line..."[2a] Seventeen double blind placebo controlled studies and 35 other reports were reviewed. There was some variability depending on the type of pain being treated. For example, fluoxetine appeared effective for chronic headaches (whereas sertraline and citalopram were not) but was not effective for neuropathic pain (while paroxetine was effective).
Other medications that may be helpful include gabapentin,³ (very well-established), carbamazepine,¹ and venlafaxine (may have the effectiveness of tricyclics while avoiding tricyclic side effects - but keep in mind that not all tricyclics are equally effective and it is unclear if venlafaxine possesses the properties of the better tricyclics).(4) Tramadol, a mu opiate receptor agonist, has recently been reported to augment antidepressant effects in patients with concomitant chronic pain syndromes.(5) Patients had failed many previous antidepressant trials alone and with potentiation. Dose was 25 mg tid for the first week and then 50 mg tid for two more weeks. Six of 12 had a good response. This drug should not be used in patients with a history of opiate addiction, as it may trigger relapse. It may also induce a withdrawal syndrome on discontinuation, and can produce seizures/ Anaphylactic reactions have occurred in patients who were allergic to codeine. Finally, anecdotal experience with the anticonvulsant topiramate suggests it may have the effectiveness in neuropathic pain that may occur with carbamazepine while having a weight loss effect that can be valuable for diabetic patients ond others whose pain is exacerbated by obesity.
If the patient is psychotic, inclusion of an antipsychotic is recommended. Review the recommendation about using an antipsychotic.
Recommendation #20 (not psychotic) or #20P (psychotic)
¹Philipp M, Flckinger M. Psychotropic drugs in the management of chronic pain syndromes. Pharmacopsychiatry 1993;26:221-234.
²Sindrup SH, Gram LF, Brosen K, et al. The SSRI paroxetine is effective in the treatment of diabetic neuropathy symptoms. Pain 1990;42:135-144.
[2a]Ansari A. The efficacy of newer antidepressants in the treatment of chronic pain: a review of current literature. Harvard Rev Psychiatry 2000;7:257-277.
(3)Backonja et al. Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus: a randomized controlled trial. JAMA 1998;280:1831-1836. Rowbotham M et al. Gabapentin for the treatment of postherpetic neuroalgia: a randomized controlled trial. JAMA 1998;280:1837-1842.
(4)Songer DA, Schulte H. Venlafaxine for the treatment of chronic pain. Am J Psychiatry 1996:153(5):737.
(5)Fanelli J, Montgomery C. Use of the analgesic tramadol in antidepressant potentiation. NCDEU Abstracts 1996, #55;
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Stimulants have been reported to be useful in the anergic depression that often accompanies medical illnesses especially in older patients.¹,²
¹Rosenberg PB, Ahmed I, Hurwitz S. Methylphenidate in depressed medically ill patients. J Clin Psychiatry 1991;52:263-267.
²Wallace AE, Kofoed LL, West AN. Double-blind, placebo-controlled trial of methylphenidate in older, depressed, medically ill patients. Am J Psychiatry 1995;152:929-931.
Recommendation #29
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